Group:MUZIC:MLP: Difference between revisions

== Cystein and glycine-rich protein 3 (CSRP3) ==

All three CSRPs are associated with the actin cytoskeleton and have similar functions in different muscle types. They up-regulate the myogenesis and have specific roles in the organisation of cytosolic structures in cardiomyocytes. It was also suggested that CSRPs may have a role in stretch sensing<ref name="r2">PMID: 12507422</ref>. MLP (CSRP3) is localized mainly in the Z-disc and the M-band of the striated muscle. Within the Z-disc, the interactions of CSRP3 with [http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Telethonin telethonin] and α-actinin2 have been reported previously<ref name="r2">PMID: 12507422</ref><ref>PMID: 16407954</ref><ref>PMID: 9341203</ref>, a more recent report however underscoring the role of CSRP3 as a scaffold protein<ref name="r3">PMID:18505755</ref>. CSRP3 has also been suggested to interact with βI-spectrin, N-RAP (Nebulin-related-anchoring protein) and cofilin2 (CFL2), underlying the essential role of CSRP3 as a scaffold protein. During myofibrilogenesis CSRP3 has been proposed to form complexes with the muscle helix-loop-helix transcription factors MyoD, MRF4 and myogenin <ref name="r3">PMID:18505755</ref>. Finally, it is involved in the anchorage of calcineurin to the Z-disc<ref>PMID: 15665106</ref>.

Mutations on the first LIM domain have been linked to familial hypertrophic cardiomyopathy (HCM). All of them ('''L44P, S54R, E55G, C58G''') are related to the proper binding of Zinc to the protein, thus causing conformational alterations. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death <ref>PMID:12642359</ref>.

The mutation '''W4R''' in CSRP3 has been reported to cause dilated cardiomyopathy (DCM) of type 1Mv. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia and patients have the risk of premature death <ref name="r2">PMID:12507422</ref>. However in more recent reports there is the suggestion that this allelic variant might actually be a common polymorphism <ref name="r3">PMID:18505755</ref><ref> PMID: 17084280</ref>.