Group:MUZIC:Myopodin: Difference between revisions
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==MYOPODIN== | ==MYOPODIN== | ||
The protein myopodin (encoded by the gene SYNPO2[http://www.uniprot.org/uniprot/Q9UMS6]), is also called genethonin-2, synaptopodin-2, synaptopodin-like and fesselin; it was first described in 2001 by Weins ''et al.'', and shown to be widely expressed in striated- and smooth-muscle cells <ref> PMID:11673475 </ref> <ref> PMID:12869577 </ref>. At least six isoforms result from alternative splicing and the size of the resulting proteins varies between 76 kDa and 136 kDa; these variants show differential tissue distribution. The discrepancy between calculated molecular mass and apparent mobility in SDS-PAGE is at present still unclear, but might be due to post-translational modifications <ref> PMID:20554076 </ref> <ref> PMID:18371299 </ref> <ref> PMID:11696420</ref> <ref> PMID:12917631 </ref> <ref> PMID:18588515 </ref>. | |||
== Function== | == Function== | ||
Myopodin is a dual compartment protein that | Myopodin is a dual compartment protein that redistributes between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced fashion, and in addition displays actin-bundling activity <ref> PMID:11673475 </ref>. | ||
In undifferentiated myoblasts, myopodin | In undifferentiated myoblasts, myopodin seems to be expressed preferentially in the nucleus and only weakly in the cytoplasm, whereas in differentiated myotubes, myopodin is incorporated into the Z-disc with no detectable nuclear expression, suggesting that myopodin may be involved in the regulation of myocyte differentiation <ref> PMID:11673475 </ref>. | ||
Myopodin has also been identified as a tumor suppressor gene that is frequently deleted in aggressive prostate cancer <ref> PMID:15111326 </ref>. Expression of myopodin protein suppresses both tumor growth and metastasis in vitro and in vivo <ref> PMID:15111326 </ref>. | Myopodin has also been identified as a tumor suppressor gene that is frequently deleted in aggressive prostate cancer <ref> PMID:15111326 </ref>. Expression of myopodin protein suppresses both tumor growth and metastasis in vitro and in vivo <ref> PMID:15111326 </ref>. | ||
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== Myopodin Interactions == | == Myopodin Interactions == | ||
Actin was the first binding partner of | Actin was the first binding partner of myopodin to be identified <ref> PMID:9314539 </ref>. Myopodin has a novel actin binding site <ref> PMID:11673475 </ref> that was identified by producing truncated fragments from myopodin and the smallest fragment that bound to F-actin contained residues 410–563 of mouse Myopodin. Actin has an essential role in anchoring Myopodin into the Z-disc <ref> PMID:11673475 </ref> <ref> PMID:17923693 </ref>. | ||
Myopodin binds to α-actinin and this interaction has been shown to involve the Spectrin filament domain repeat region of α-actinin <ref> PMID:16450054 </ref>. It's believed that synaptopodin family members are involved in the organization and anchoring of actin in the cell and might be necessary 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>. | Myopodin binds to α-actinin and this interaction has been shown to involve the Spectrin filament domain repeat region of α-actinin <ref> PMID:16450054 </ref>. It's believed that synaptopodin family members are involved in the organization and anchoring of actin in the cell and might be necessary 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 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>. | ||