SYNPO2

Myopodin protein, also called Synaptopodin-2 is a protein that in humans is encoded by the SYNPO2 gene.^[1][2][3] Myopodin is expressed in cardiac, smooth muscle and skeletal muscle, and localizes to Z-disc structures.

Structure

Myopodin is a 117.4 kDa protein composed of 1093 amino acids,^[4] although four alternatively-spliced isoforms have been described.^[5] Myopodin contains one PPXY motif, multiple PXXP motifs, and two potential nuclear localization sequences (one N-terminal and one C-terminal).^[1] PPXY motifs have been shown to mediate interactions, and PXXP motifs represent potential sites of interaction for SH3 domain-containing proteins. Myopodin contains a novel actin binding site (between amino acids 410 and 563) in the center of the protein.^[1]

Function

During myotube differentiation, myopodin interacts with stress fibers prior to co-localizing with alpha actinin-2 at Z-discs in mature striated muscle cells.^[1] Myopodin has been shown to shuttle between the nucleus and cytoplasm in myoblasts and myotubes in response to stress; its export from the nucleus is sensitive to lemtomycin B.^[1] The nuclear localization of myopodin is sensitive to Importin 13, which directly binds myopodin and facilitates its translocation.^[6] Importin binding and nuclear import of myopodin appears to be mediated by serine/threonine phosphorylation-dependent binding of myopodin to 14-3-3 beta ^[7] Myopodin appears to regulate compartmentalized, intracellular signal transduction between the Z-disc and nucleus in cardiac muscle cells, by forming a Z-disc signaling complex with alpha actinin-2, calcineurin, CaMKII, muscle-specific A-kinase anchoring protein, and myomegalin.^[8] Specifically, phosphorylation by protein kinase A or CaMKII, and dephosphorylation by calcineurin facilitates the binding or release, respectively, of 14-3-3-beta, and the corresponding nuclear or cytoplasmic localization, respectively, of myopodin.^[8]

Interactions

Myopodin interacts with:

References

Further reading