Group:MUZIC:Myozenin
From Proteopedia
(→FATZ binding partners) |
|||
| Line 10: | Line 10: | ||
== FATZ binding partners== | == FATZ binding partners== | ||
| - | Different interacting partners of FATZ have been characterized by cellular and biochemical approaches. Screenings of yeast two-hybrid assays allowed identifying interactions with α-actinin-2, filamin-C, myotilin, teletonin, calcineurin and ZASP/Cypher( in general Enigma family protein).<ref>PMID: 11171996</ref><ref>PMID: 11842093</ref><ref></ref><ref>PMID: 16076904</ref><ref>PMID: 11114196</ref><ref>PMID: 10984498</ref> | + | Different interacting partners of FATZ have been characterized by cellular and biochemical approaches. Screenings of yeast two-hybrid assays allowed identifying interactions with α-actinin-2, filamin-C, myotilin, teletonin, calcineurin and ZASP/Cypher( in general Enigma family protein).<ref>PMID: 11171996</ref><ref>PMID: 11842093</ref><ref>PMID: 19047374</ref><ref>PMID: 16076904</ref><ref>PMID: 11114196</ref><ref>PMID: 10984498</ref> |
Most of the mapping of the binding regions where done by screening deletants library with the yeast two-hybrid assays and furthermore confirmed by co-immunoprecipitation or pull down assays. Many interacting partners have their binding sites in the C-terminal of FATZs while others in the N-terminal region. Moreover, in some cases as for a-actinin-2 and filamin-C, occur competitively binding<ref></ref>. | Most of the mapping of the binding regions where done by screening deletants library with the yeast two-hybrid assays and furthermore confirmed by co-immunoprecipitation or pull down assays. Many interacting partners have their binding sites in the C-terminal of FATZs while others in the N-terminal region. Moreover, in some cases as for a-actinin-2 and filamin-C, occur competitively binding<ref></ref>. | ||
Revision as of 21:54, 3 July 2011
Contents |
FATZ
The filamin-C alpha-actinin telethonin Z-disc binding protein ( FATZ) is a protein family of three isoforms expressed in muscle cells.[1] This protein family (also known as Myozenin or Calsarcin) is mainly localized in the Z-disc, although recently it has been described that FATZ-2 was found in cardiac nuclei. [2] The expression of the three isoforms has been shown to be fibre type specific as for instance: the members FATZ-1 and FATZ-3 are highly expressed in skeletal muscle fast twitch fibers while FATZ-2 is predominantly expressed in cardiac muscle slow-twitch fibers.[3][4] Nevertheless, the three isoforms seems to have redundant function since all the three are sharing the same binding partners. Due to its Z-disc localization and multiple binding partners, FATZ can be considered as an adaptor molecule that support and maintains the Z-disc architecture. But on the other hand, its interaction with calcineurin involves this protein family in a signalling pathway controlling the cell response to pressure overload.[5] Therefore, the FATZ protein family could be seen as one example of Z-disc proteins where signalling and structural support converge.
Structure
There is not prediction of canonical domains in the tertiary structure of FATZ. Nevertheless, based on the prediction of secondary elements, it has been identify three regions on the sequence of FATZ-1: N-terminal CD1( 1-75), glycine rich domain(75-171) and C-terminal CD 2( 172-299). [6] But, currently there is no tridimensional model for the structure of any of the isoforms.
FATZ binding partners
Different interacting partners of FATZ have been characterized by cellular and biochemical approaches. Screenings of yeast two-hybrid assays allowed identifying interactions with α-actinin-2, filamin-C, myotilin, teletonin, calcineurin and ZASP/Cypher( in general Enigma family protein).[7][8][9][10][11][12]
Most of the mapping of the binding regions where done by screening deletants library with the yeast two-hybrid assays and furthermore confirmed by co-immunoprecipitation or pull down assays. Many interacting partners have their binding sites in the C-terminal of FATZs while others in the N-terminal region. Moreover, in some cases as for a-actinin-2 and filamin-C, occur competitively bindingCite error: Invalid <ref> tag;
refs with no name must have content.
FATZ association with hypertrophic cardiomyopathy
In experimental models, it has been shown that the absence of FATZ-2 led to up-regulation of calcineurin phosphatase activity and cellular proliferation, thereby inducing hyperthrophic cardiomyopathy. Cite error: Invalid <ref> tag;
refs with no name must have content Moreover, the study of families this disease has suggested that mutations X and Y in FAT-2 where associated with the pathology. [13]Nevertheless, another study has also shown that there was no correlation between the suggested mutations and the disease. Cite error: Invalid <ref> tag;
refs with no name must have content. Given that, whether FATZ-2 is a marker of hypertrophic cardiomyopathy or not is still under discussion and more studies shall be done to clearly define its physiological role in cardiomyocites.
