Group:MUZIC:MLP: Difference between revisions

Line 13:

== 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.

All three CSRPs 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<ref>PMID: 12507422</ref>, 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.

The interactions of MLP with telethonin has been reported previously<ref>PMID: 12507422</ref>, <ref>16407954</ref>, however recent reports demonstrate that this interaction is not existing <ref>PMID:18505755</ref>.

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]~~<ref>PMID: 12507422</ref> ~~and~~ is ~~responsible for Dilated Cardiomyopathy (~~DCM)

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 of type 1Mv(DCM). 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>PMID:12507422</ref>. However a more recent report demonstrates that the W4R mutation is not sufficient to cause DCM <ref>PMID:18505755</ref>.

== References ==

@@ Line 13: / Line 13: @@
 == 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.
+All three CSRPs 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<ref>PMID: 12507422</ref>, 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.
+The interactions of MLP with telethonin has been reported previously<ref>PMID: 12507422</ref>, <ref>16407954</ref>, however recent reports demonstrate that this interaction is not existing <ref>PMID:18505755</ref>.
+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]<ref>PMID: 12507422</ref> and is responsible for Dilated Cardiomyopathy (DCM)
+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 of type 1Mv(DCM). 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>PMID:12507422</ref>. However a more recent report demonstrates that the W4R mutation is not sufficient to cause DCM <ref>PMID:18505755</ref>.
 == References ==