Group:MUZIC:Myopodin: Difference between revisions

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Actin was the first binding partner of myopodin to be identified. Actin binding was narrowed down to residues 410–563 of murine myopodin <ref> PMID:11673475 </ref>.

Myopodin also binds to α-actinin via its spectrin repeats <ref> PMID:16450054 </ref>, <ref> PMID:20554076 </ref> . Myopodin may be generally involved in the organization and anchoring of actin in muscle cells and might be required for the correct localization of α-actinin. This hypothesis is supported by recent findings where myopodin expression precedes actin and α-actinin expression <ref> PMID:20554076 </ref>.

A ~~newly identiﬁed~~ filamin-binding region ~~within the molecule was reported by performing yeast two-hybrid assays using carboxy-terminally and/or amino-terminally truncated constructs <ref> PMID:20554076 </ref>. The interaction~~ was mapped to a fragment encompassing amino acids 240–521 of ~~Myopodin~~, i.e. a region that contains two of the previously described homology regions shared by myopodin and synaptopodin <ref> PMID:~~11696420~~ </ref>. The alternative transcription offers the possibility of expression of two isoforms of Myopodin, which probably differ in their binding properties for these PDZ binding domain detected, however, there is preliminary evidence that the PDZ binding domain from Myopodin interacts with the C terminal part of Synemin <ref> PMID:16631741 </ref>.

A filamin-binding region was mapped to a fragment encompassing amino acids 240–521 of myopodin, i.e. a region that contains two of the previously described homology regions shared by myopodin and synaptopodin <ref> PMID:20554076 </ref>.

The alternative transcription offers the possibility of expression of two isoforms of Myopodin, which probably differ in their binding properties for these PDZ binding domain detected, however, there is preliminary evidence that the PDZ binding domain from Myopodin interacts with the C terminal part of Synemin <ref> PMID:16631741 </ref>.

Through yeast two-hybrid analysis, was found the interaction between Myopodin and Zyxin both in vitro and in vivo and that this interaction leads to slower migration of prostate cancer cells and reduced invasiveness <ref> PMID:16885336 </ref>.

In cardiomyocytes, Myopodin forms a Z-disc signaling complex with α-Actinin, Calcineurin, Ca2+/calmodulin-dependent kinase II (CaMKII), Muscle-specific A-kinase anchoring protein, and Myomegalin. Calcineurin keeps Myopodin dephosphorylated preventing 14-3-3ß binding to myopodin. Upon activation of PKA/CaMKII or inhibition of Calcineurin, Myopodin undergoes phosphorylation, enabling its interaction with 14-3-3ß, which releases Myopodin from the Z-disc-anchoring proteins and induces its nuclear import. This novel intracellular signaling pathway suggests that changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart <ref> PMID:17923693 </ref>.

@@ Line 17: / Line 17: @@
 Actin was the first binding partner of myopodin to be identified. Actin binding was narrowed down to residues 410–563 of murine myopodin <ref> PMID:11673475 </ref>.
 Myopodin also binds to α-actinin via its spectrin repeats <ref> PMID:16450054 </ref>, <ref> PMID:20554076 </ref> . Myopodin may be generally involved in the organization and anchoring of actin in muscle cells and might be required for the correct localization of α-actinin. This hypothesis is supported by recent findings where myopodin expression precedes actin and α-actinin expression <ref> PMID:20554076 </ref>.
-A newly identiﬁed filamin-binding region within the molecule was reported by performing yeast two-hybrid assays using carboxy-terminally and/or amino-terminally truncated constructs <ref> PMID:20554076 </ref>. The interaction was mapped to a fragment encompassing amino acids 240–521 of Myopodin, i.e. a region that contains two of the previously described homology regions shared by myopodin and synaptopodin <ref> PMID:11696420 </ref>. The alternative transcription offers the possibility of expression of two isoforms of Myopodin, which probably differ in their binding properties for these PDZ binding domain detected, however, there is preliminary evidence that the PDZ binding domain from Myopodin interacts with the C terminal part of Synemin <ref> PMID:16631741 </ref>.
+A filamin-binding region was mapped to a fragment encompassing amino acids 240–521 of myopodin, i.e. a region that contains two of the previously described homology regions shared by myopodin and synaptopodin <ref> PMID:20554076 </ref>.
+The alternative transcription offers the possibility of expression of two isoforms of Myopodin, which probably differ in their binding properties for these PDZ binding domain detected, however, there is preliminary evidence that the PDZ binding domain from Myopodin interacts with the C terminal part of Synemin <ref> PMID:16631741 </ref>.
 Through yeast two-hybrid analysis, was found the interaction between Myopodin and Zyxin both in vitro and in vivo and that this interaction leads to slower migration of prostate cancer cells and reduced invasiveness <ref> PMID:16885336 </ref>.
 In cardiomyocytes, Myopodin forms a Z-disc signaling complex with α-Actinin, Calcineurin, Ca2+/calmodulin-dependent kinase II (CaMKII), Muscle-specific A-kinase anchoring protein, and Myomegalin. Calcineurin keeps Myopodin dephosphorylated preventing 14-3-3ß binding to myopodin. Upon activation of PKA/CaMKII or inhibition of Calcineurin, Myopodin undergoes phosphorylation, enabling its interaction with 14-3-3ß, which releases Myopodin from the Z-disc-anchoring proteins and induces its nuclear import. This novel intracellular signaling pathway suggests that changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart <ref> PMID:17923693 </ref>.