Group:MUZIC:Myozenin - Revision history

Jaime Prilusky at 11:27, 1 July 2015

Jaime Prilusky — Wed, 01 Jul 2015 11:27:11 GMT

←Older revision		Revision as of 11:27, 1 July 2015
Line 23:		Line 23:
	==References==		==References==
	<references/>		<references/>
		+
		+	[[Category: Z-disk]]

Ariadna Rodriguez-Chamorro: /* Function and Interactions */

Ariadna Rodriguez-Chamorro — Mon, 25 Feb 2013 20:40:04 GMT

Function and Interactions

←Older revision		Revision as of 20:40, 25 February 2013
Line 13:		Line 13:
	The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.		The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.

-	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the Calcineurin/NFAT pathway in striated muscle. The activation of the Calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle, and also the hypertrophic response to pressure overload in cardiac muscle. The isoform FATZ-1 is a negative regulator of the Calcineurin/NFAT pathway in fast-twitch fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise <ref>PMID: ~~2564612~~</ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where the absence of FATZ-2 leads to hypertrophy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.	+	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the Calcineurin/NFAT pathway in striated muscle. The activation of the Calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle, and also the hypertrophic response to pressure overload in cardiac muscle. The isoform FATZ-1 is a negative regulator of the Calcineurin/NFAT pathway in fast-twitch fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise <ref>PMID: 18846255 </ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where the absence of FATZ-2 leads to hypertrophy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.

	== Pathology==		== Pathology==

Ariadna Rodriguez-Chamorro: /* Function and Interactions */

Ariadna Rodriguez-Chamorro — Tue, 05 Feb 2013 23:31:05 GMT

Function and Interactions

←Older revision		Revision as of 23:31, 5 February 2013
Line 9:		Line 9:
	== Function and Interactions==		== Function and Interactions==

-	[[Image:FATZ_binding_map.jpg\|550px\|left\|thumb\|Binding regions on FATZ proteins]]The three protein members of the FATZ family have a plethora of interacting partners which are additionally shared by all of them. As shown by the figure on the right, they interact with several Z-disc proteins. For instance: α-actinin-2, filamin-C, myotilin, telethonin, calcineurin and ZASP/Cypher (in general the Enigma protein family) <ref name="r2">PMID: 11171996</ref><ref name="r4">PMID: 11842093</ref><ref>PMID: 19047374</ref><ref>PMID: 16076904</ref><ref name="r3">PMID: 11114196</ref><ref name="r1">PMID: 10984498</ref>. In general, those interactions and their binding regions were found by yeast two-hybrid assays, co-immunoprecipitation, and pull down assays.	+	[[Image:FATZ_binding_map.jpg\|550px\|left\|thumb\|Binding regions on FATZ proteins]]The three protein members of the FATZ family have a plethora of interacting partners which are additionally shared by all of them. As shown by the figure on the right, they interact with several Z-disc proteins. For instance: α-actinin-2, filamin-C, myotilin, telethonin, calcineurin and ZASP/Cypher (in general the Enigma protein family, [[http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Enigma_Family]]) <ref name="r2">PMID: 11171996</ref><ref name="r4">PMID: 11842093</ref><ref>PMID: 19047374</ref><ref>PMID: 16076904</ref><ref name="r3">PMID: 11114196</ref><ref name="r1">PMID: 10984498</ref>. In general, those interactions and their binding regions were found by yeast two-hybrid assays, co-immunoprecipitation, and pull down assays.

	The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.		The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.

Ariadna Rodriguez-Chamorro: /* Pathology */

Ariadna Rodriguez-Chamorro — Tue, 05 Feb 2013 23:10:02 GMT

Pathology

←Older revision		Revision as of 23:10, 5 February 2013
Line 17:		Line 17:
	== Pathology==		== Pathology==

-	FATZ-2 knockdown mouse hearts, subjected to pressure overload, over-~~activate~~ the Calcineurin/NFAT pathway. Consequently, they ~~show~~ hypertrophic hearts and developed cardiomyopathy. The transgenic over-expression of FATZ-2 ~~rescue~~ the mouse hearts from hypertrophic agonists, suggesting that FATZ-2 could be a gene ~~affected~~ in patients with the same ~~disease~~ <ref name="r5">PMID: 15543153</ref>. Later on, the investigation of two families with ~~clinical symptoms of~~ hypertrophic cardiomyopathy(HCM) ~~suggested~~ that mutations ~~S48P and I246M~~ in FATZ-2 ~~were associated with familial HCM~~ <ref>PMID: 17347475 </ref>. However, ~~another~~ study on 438 ~~patiens~~ concluded that mutations in FATZ-2 were rare causes of familial HCM <ref>PMID: 18591919</ref>.	+	FATZ-2 knockdown mouse hearts, subjected to pressure overload, over-activated the Calcineurin/NFAT pathway. Consequently, they showed hypertrophic hearts and developed cardiomyopathy. The transgenic over-expression of FATZ-2 rescued the mouse hearts from the disease, even when treated with hypertrophic agonists, suggesting that FATZ-2 could be an affected gene in patients with the same condition <ref name="r5">PMID: 15543153</ref>. Later on, the investigation of two families with hypertrophic cardiomyopathy(HCM) found that two mutations in FATZ-2: S48P and I246M, could be responsible for the disease <ref>PMID: 17347475 </ref>. However, a study on 438 patients concluded that those mutations in FATZ-2 were rare causes of familial HCM <ref>PMID: 18591919</ref>.

-	A recent study of the mutants S48P and I246M in mouse models showed that the animals develop the clinical symptoms of HCM, myofibrillar disarray and Z-disc structural abnormalities. ~~However~~, it was not observed any over-activity of the Calcineurin/NFAT pathway, ~~suggesting~~ that HCM caused by those mutations is not associated with the negative regulation of FATZ-2 over Calcineurin <ref>PMID: 22987565</ref>. These findings suggest that FATZ-2 might modulate the activity of other proteins, also involved in the hypertrophy response to pressure overload.	+	A recent study of the mutants S48P and I246M in mouse models showed that the animals develop the clinical symptoms of HCM, myofibrillar disarray and Z-disc structural abnormalities. In contrast, it was not observed any over-activity of the Calcineurin/NFAT pathway, revealing that HCM caused by those mutations is not associated with the negative regulation of FATZ-2 over Calcineurin <ref>PMID: 22987565</ref>. These findings suggest that FATZ-2 might modulate the activity of other proteins, also involved in pathways controlling the hypertrophy response to pressure overload.

	==References==		==References==
	<references/>		<references/>

Ariadna Rodriguez-Chamorro: /* Pathology */

Ariadna Rodriguez-Chamorro — Tue, 05 Feb 2013 23:00:08 GMT

Pathology

←Older revision		Revision as of 23:00, 5 February 2013
Line 17:		Line 17:
	== Pathology==		== Pathology==

-	FATZ-2 knockdown mouse hearts subjected to pressure overload over-activate the Calcineurin/NFAT pathway~~, consequently~~, they show hypertrophic hearts and developed cardiomyopathy. The transgenic over-expression of FATZ-2 rescue the mouse hearts from hypertrophic agonists, suggesting that FATZ-2 could be a gene affected in patients with the same disease <ref name="r5">PMID: 15543153</ref>. Later on, the investigation of two families with clinical symptoms of hypertrophic cardiomyopathy(HCM) suggested that mutations S48P and I246M in FATZ-2 were associated with familial HCM <ref>PMID: 17347475 </ref>. However, another study on 438 patiens concluded that mutations in FATZ-2 were rare causes of familial HCM <ref>PMID: 18591919</ref>.	+	FATZ-2 knockdown mouse hearts, subjected to pressure overload, over-activate the Calcineurin/NFAT pathway. Consequently, they show hypertrophic hearts and developed cardiomyopathy. The transgenic over-expression of FATZ-2 rescue the mouse hearts from hypertrophic agonists, suggesting that FATZ-2 could be a gene affected in patients with the same disease <ref name="r5">PMID: 15543153</ref>. Later on, the investigation of two families with clinical symptoms of hypertrophic cardiomyopathy(HCM) suggested that mutations S48P and I246M in FATZ-2 were associated with familial HCM <ref>PMID: 17347475 </ref>. However, another study on 438 patiens concluded that mutations in FATZ-2 were rare causes of familial HCM <ref>PMID: 18591919</ref>.

	A recent study of the mutants S48P and I246M in mouse models showed that the animals develop the clinical symptoms of HCM, myofibrillar disarray and Z-disc structural abnormalities. However, it was not observed any over-activity of the Calcineurin/NFAT pathway, suggesting that HCM caused by those mutations is not associated with the negative regulation of FATZ-2 over Calcineurin <ref>PMID: 22987565</ref>. These findings suggest that FATZ-2 might modulate the activity of other proteins, also involved in the hypertrophy response to pressure overload.		A recent study of the mutants S48P and I246M in mouse models showed that the animals develop the clinical symptoms of HCM, myofibrillar disarray and Z-disc structural abnormalities. However, it was not observed any over-activity of the Calcineurin/NFAT pathway, suggesting that HCM caused by those mutations is not associated with the negative regulation of FATZ-2 over Calcineurin <ref>PMID: 22987565</ref>. These findings suggest that FATZ-2 might modulate the activity of other proteins, also involved in the hypertrophy response to pressure overload.

Ariadna Rodriguez-Chamorro: /* Pathology */

Ariadna Rodriguez-Chamorro — Tue, 05 Feb 2013 22:58:20 GMT

Pathology

←Older revision		Revision as of 22:58, 5 February 2013
Line 17:		Line 17:
	== Pathology==		== Pathology==

-	~~It was shown that~~ FATZ-2 KO mouse hearts subjected to pressure overload ~~chronically activated~~ the ~~calcineurin~~/NFAT ~~signalling~~ pathway~~. In consequence~~, ~~those animals showed~~ hypertrophic hearts and developed cardiomyopathy. ~~Moreover, the~~ transgenic over-expression of FATZ-2 ~~rescued~~ the mouse hearts from ~~angiotensin II-induced cardiac hypertrophy~~, ~~which suggested~~ that FATZ-2 could be a ~~target~~ gene affected in patients with the same disease<ref name="r5">PMID: 15543153</ref>. Later on, the investigation of two families with clinical symptoms of hypertrophic cardiomyopathy(HCM) suggested that mutations S48P and I246M in FATZ-2 ~~where~~ associated with familial HCM<ref>PMID: 17347475 </ref>. However, another study on 438 patiens concluded that mutations in FATZ-2 were rare causes of familial HCM <ref>PMID: 18591919</ref>. ~~Recently, a set~~ of ~~experiments in mice models expressing~~ the mutants ~~FATZ-2~~ S48P and I246M showed the clinical symptoms of HCM, myofibrillar disarray and Z-disc structural abnormalities. However, ~~no upregulation~~ of the ~~calcineurin~~/NFAT ~~signalling~~ pathway ~~was observed~~, suggesting that HCM caused by those mutations is not associated to the ~~inhibitory effect~~ of FATZ-2 ~~on calcineurin~~ <ref>PMID: 22987565</ref>.	+	FATZ-2 knockdown mouse hearts subjected to pressure overload over-activate the Calcineurin/NFAT pathway, consequently, they show hypertrophic hearts and developed cardiomyopathy. The transgenic over-expression of FATZ-2 rescue the mouse hearts from hypertrophic agonists, suggesting that FATZ-2 could be a gene affected in patients with the same disease <ref name="r5">PMID: 15543153</ref>. Later on, the investigation of two families with clinical symptoms of hypertrophic cardiomyopathy(HCM) suggested that mutations S48P and I246M in FATZ-2 were associated with familial HCM <ref>PMID: 17347475 </ref>. However, another study on 438 patiens concluded that mutations in FATZ-2 were rare causes of familial HCM <ref>PMID: 18591919</ref>.
		+
		+	A recent study of the mutants S48P and I246M in mouse models showed that the animals develop the clinical symptoms of HCM, myofibrillar disarray and Z-disc structural abnormalities. However, it was not observed any over-activity of the Calcineurin/NFAT pathway, suggesting that HCM caused by those mutations is not associated with the negative regulation of FATZ-2 over Calcineurin <ref>PMID: 22987565</ref>. These findings suggest that FATZ-2 might modulate the activity of other proteins, also involved in the hypertrophy response to pressure overload.

	==References==		==References==
	<references/>		<references/>

Ariadna Rodriguez-Chamorro: /* Function and Interactions */

Ariadna Rodriguez-Chamorro — Tue, 05 Feb 2013 22:32:31 GMT

Function and Interactions

←Older revision		Revision as of 22:32, 5 February 2013
Line 13:		Line 13:
	The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.		The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.

-	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the Calcineurin/NFAT pathway in striated muscle. The activation of the Calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle, and also the hypertrophic response to pressure overload in cardiac muscle. The isoform FATZ-1 is a negative regulator of the Calcineurin/NFAT pathway in fast-twitch fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise <ref>PMID: 2564612</ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where FATZ-2 ~~absence~~ leads to hypertrophy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.	+	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the Calcineurin/NFAT pathway in striated muscle. The activation of the Calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle, and also the hypertrophic response to pressure overload in cardiac muscle. The isoform FATZ-1 is a negative regulator of the Calcineurin/NFAT pathway in fast-twitch fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise <ref>PMID: 2564612</ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where the absence of FATZ-2 leads to hypertrophy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.

	== Pathology==		== Pathology==

Ariadna Rodriguez-Chamorro: /* Function and Interactions */

Ariadna Rodriguez-Chamorro — Tue, 05 Feb 2013 22:31:11 GMT

Function and Interactions

←Older revision		Revision as of 22:31, 5 February 2013
Line 13:		Line 13:
	The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.		The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.

-	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the ~~calcineurin~~/NFAT pathway in striated muscle. The activation of the ~~calcineurin~~/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle and the hypertrophic response to pressure overload in cardiac muscle. The isoform FATZ-1 is a negative regulator of the Calcineurin/NFAT pathway in fast-twitch fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise <ref>PMID: 2564612</ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where FATZ-2 absence leads to hypertrophy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.	+	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the Calcineurin/NFAT pathway in striated muscle. The activation of the Calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle, and also the hypertrophic response to pressure overload in cardiac muscle. The isoform FATZ-1 is a negative regulator of the Calcineurin/NFAT pathway in fast-twitch fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise <ref>PMID: 2564612</ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where FATZ-2 absence leads to hypertrophy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.

	== Pathology==		== Pathology==

Ariadna Rodriguez-Chamorro: /* Function and Interactions */

Ariadna Rodriguez-Chamorro — Tue, 05 Feb 2013 22:29:31 GMT

Function and Interactions

←Older revision		Revision as of 22:29, 5 February 2013
Line 13:		Line 13:
	The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.		The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.

-	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the calcineurin/NFAT pathway in striated muscle. The activation of the calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle. The isoform FATZ-1 ~~(Calsarcin-2 and Myozenin-1)~~ is a negative regulator of the Calcineurin/NFAT pathway in fast fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT ~~signaling~~ pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise~~. The interaction between FATZ-1 and Calcineurin is another check point in the signaling pathways controlling skeletal muscle fiber type composition and response to exercise performance~~ <ref>PMID: 2564612</ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where FATZ-2 absence leads to ~~hypertropy~~ in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.	+	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the calcineurin/NFAT pathway in striated muscle. The activation of the calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle and the hypertrophic response to pressure overload in cardiac muscle. The isoform FATZ-1 is a negative regulator of the Calcineurin/NFAT pathway in fast-twitch fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise <ref>PMID: 2564612</ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where FATZ-2 absence leads to hypertrophy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.

	== Pathology==		== Pathology==

Ariadna Rodriguez-Chamorro: /* Function and Interactions */

Ariadna Rodriguez-Chamorro — Tue, 05 Feb 2013 22:25:57 GMT

Function and Interactions

←Older revision		Revision as of 22:25, 5 February 2013
Line 13:		Line 13:
	The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.		The interaction of FATZ-1 with α-actinin-2 has been reported on the CD2 domain of all FATZ proteins<ref name="r1">PMID: 10984498</ref><ref name="r2">PMID: 11171996 </ref><ref name="r4">PMID: 11842093</ref>. The data suggest a binding interface on α-actinin-2 spanning the spectrin repeat domains SR2,SR3 and SR4. FATZ-1, α-actinin-2 and myotilin appear in premyofibrils, when there is no Z-disc but a small structure called Z-body. In addition, the complexes FATZ-1::α-actinin-2, FATZ-1::myotilin and myotilin::α-actinin-2 are observed in that early stages. In contrast, telethonin localized to the Z-disc in later stages and the complex FATZ-1::telethonin was only observed in mature myofibrils. These findings suggest that the interactions of FATZ-1 with α-actinin-2 and myotilin are very important for the initiation of the Z-disc assembly. Besides, it is hypothesized that FATZ-1 should undergone conformational changes during myofibrilogenesis to interact with telethonin. Thus, telethonin incorporation to the the Z-disc depends to FATZ-1 viability <ref> PMID: 15810059 </ref> . It is suggested that FATZ-1 performs other functions, like bridging filamin-C and α-actinin-2. However, a competitive binding assay showed that α-actinin-2 displaces filamin-C from FATZ-1. Therefore, it still remains an open question whether a ternary complex could exist and what its physiological role would be <ref name="r2">PMID: 11171996</ref>.

-	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the calcineurin/NFAT pathway in striated muscle. The activation of the calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle. The isoform FATZ-1 (Calsarcin-2 and Myozenin-1) is a negative regulator of the Calcineurin/NFAT pathway in fast fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT signaling pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise. The interaction between FATZ-1 and Calcineurin is another check point in the signaling pathways controlling skeletal muscle fiber type composition and response to exercise performance <ref>PMID: 2564612</ref>. FATZ-2 is a negative regulator of Calcineurin in ~~cardiac muscle~~, ~~which~~ absence ~~from cardiomyocites~~ leads to hypertropy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.	+	Both proteins, FATZ-1 and FATZ-2 are negative regulators of the calcineurin/NFAT pathway in striated muscle. The activation of the calcineurin/NFAT pathway determines the switch to slow-twitch fiber phenotype in skeletal muscle. The isoform FATZ-1 (Calsarcin-2 and Myozenin-1) is a negative regulator of the Calcineurin/NFAT pathway in fast fibers. In absence of FATZ-1 the activity of the Calcineurin/NFAT signaling pathway increases, consequently, there are a major number of oxidative fibers, and less fatigue of FATZ-1 knockdown compared to FATZ-1 wild type mice subjected to long endurance exercise. The interaction between FATZ-1 and Calcineurin is another check point in the signaling pathways controlling skeletal muscle fiber type composition and response to exercise performance <ref>PMID: 2564612</ref>. FATZ-2 is a negative regulator of Calcineurin in cardiomyocytes, where FATZ-2 absence leads to hypertropy in response to pressure overload and hypertrophic agonists <ref>PMID: 15543153</ref>.

	== Pathology==		== Pathology==