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Introduction
The Cystein and glycine-rich protein 3 (CSRP3), or as also known as Muscle LIM Protein (MLP), is one of the three CSRP family members identified in vertebrates. CSRP3 has been identified muscle and cardiac cells[1]. The three family members contain 192-194 residues and two LIM domains adjacent to a flexible glycine-rich linker. Each LIM domain comprises two Zn-binding motifs CCHC and CCCC representing a structural and presumably functional independent unit.
Sequence Annotation
CSRP3 comprises 194 aminoacids with two LIM domains followed by glycine reach sequences | Pubmed(CSRP3_HUMAN).
Structures
LIM domains have been intensively characterized using NMR. The two LIM domains of CSRP3 have been also determined by NMR (| LIM1: 2O10 and | LIM2: 2O13 )
Function and Interactions
All three CRPs are associated with the actin cytoskeleton and have similar functions in different muscle varieties. CSRP3 is localized in Z and M-lines in striated muscles.
The interactions of MLP with α-actinin, telethonin[2], βI-spectrin, N-RAP (Nebulin-related-anchoring protein) and cofilin2 (CFL2) have been suggested in the literature, underlying the essential role of MLP as a scaffold protein in the sarcomere. During myogenesis MLP has been suggested to form complexes with the muscle helix-loop-helix transcription factors MyoD, MRF4 and myogenin.
Pathology
Mutations on MLP are reported to be involved in cardiac myopathies. The MLP mutation W4R is disrupting the interaction with [telethonin][3] and is responsible for Dilated Cardiomyopathy (DCM)
References
- ↑ Fung YW, Wang RX, Heng HH, Liew CC. Mapping of a human LIM protein (CLP) to human chromosome 11p15.1 by fluorescence in situ hybridization. Genomics. 1995 Aug 10;28(3):602-3. PMID:7490106 doi:http://dx.doi.org/10.1006/geno.1995.1200
- ↑ Knoll R, Hoshijima M, Hoffman HM, Person V, Lorenzen-Schmidt I, Bang ML, Hayashi T, Shiga N, Yasukawa H, Schaper W, McKenna W, Yokoyama M, Schork NJ, Omens JH, McCulloch AD, Kimura A, Gregorio CC, Poller W, Schaper J, Schultheiss HP, Chien KR. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell. 2002 Dec 27;111(7):943-55. PMID:12507422
- ↑ Knoll R, Hoshijima M, Hoffman HM, Person V, Lorenzen-Schmidt I, Bang ML, Hayashi T, Shiga N, Yasukawa H, Schaper W, McKenna W, Yokoyama M, Schork NJ, Omens JH, McCulloch AD, Kimura A, Gregorio CC, Poller W, Schaper J, Schultheiss HP, Chien KR. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell. 2002 Dec 27;111(7):943-55. PMID:12507422
Additional References
- Gehmlich K, Ehler E, Perrot A, Furst DO, Geier C. "MLP: A Stress Sensor Goes Nuclear" by Sylvia Gunkel, Jorg Heineke, Denise Hilfiker-Kleiner, Ralph Knoll, J Mol Cell Cardiol. 2009;47(4):423-5. J Mol Cell Cardiol. 2010 Feb;48(2):424-5; author reply 426-7. Epub 2009, Oct 30. PMID:19879879 doi:10.1016/j.yjmcc.2009.10.021
- Gehmlich K, Geier C, Milting H, Furst D, Ehler E. Back to square one: what do we know about the functions of muscle LIM protein in the heart? J Muscle Res Cell Motil. 2008;29(6-8):155-8. Epub 2008 Dec 30. PMID:19115046 doi:10.1007/s10974-008-9159-4
- Knoll R, Kostin S, Klede S, Savvatis K, Klinge L, Stehle I, Gunkel S, Kotter S, Babicz K, Sohns M, Miocic S, Didie M, Knoll G, Zimmermann WH, Thelen P, Bickeboller H, Maier LS, Schaper W, Schaper J, Kraft T, Tschope C, Linke WA, Chien KR. A common MLP (muscle LIM protein) variant is associated with cardiomyopathy. Circ Res. 2010 Mar 5;106(4):695-704. Epub 2009 Dec 31. PMID:20044516 doi:10.1161/CIRCRESAHA.109.206243
- Schallus T, Edlich C, Stier G, Muhle-Goll C. 1H, 13C, and 15N assignment of the muscular LIM protein MLP/CRP3. Biomol NMR Assign. 2007 Jul;1(1):41-3. Epub 2007 May 10. PMID:19636821 doi:10.1007/s12104-007-9010-7
- Knoll R, Hoshijima M, Hoffman HM, Person V, Lorenzen-Schmidt I, Bang ML, Hayashi T, Shiga N, Yasukawa H, Schaper W, McKenna W, Yokoyama M, Schork NJ, Omens JH, McCulloch AD, Kimura A, Gregorio CC, Poller W, Schaper J, Schultheiss HP, Chien KR. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell. 2002 Dec 27;111(7):943-55. PMID:12507422
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