Myopodin is a 117.4 kDa protein composed of 1093 amino acids,[ 8] although four alternatively-spliced isoforms have been described.[ 9] Myopodin contains one PPXY motif, multiple PXXP motifs, and two potential nuclear localization sequences (one N-terminal and one C-terminal ).[ 5] 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.[ 5]
During myotube differentiation, myopodin interacts with stress fibers prior to co-localizing with alpha actinin-2 at Z-discs in mature striated muscle cells.[ 5] 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 .[ 5] 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 [ 10] 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 .[ 11] 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.[ 11]
^ a b c GRCh38: Ensembl release 89: ENSG00000172403 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000050315 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ a b c d e f g Weins A, Schwarz K, Faul C, Barisoni L, Linke WA, Mundel P (Oct 2001). "Differentiation- and stress-dependent nuclear cytoplasmic redistribution of myopodin, a novel actin-bundling protein" . The Journal of Cell Biology . 155 (3): 393–404. doi :10.1083/jcb.200012039 . PMC 2150840 . PMID 11673475 .
^ a b c Liang J, Ke G, You W, Peng Z, Lan J, Kalesse M, Tartakoff AM, Kaplan F, Tao T (Jan 2008). "Interaction between importin 13 and myopodin suggests a nuclear import pathway for myopodin". Molecular and Cellular Biochemistry . 307 (1–2): 93–100. doi :10.1007/s11010-007-9588-1 . PMID 17828378 . S2CID 19273082 .
^ "Entrez Gene: SYNPO2 synaptopodin 2" .
^ Joon-Sub Chung. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information" . heartproteome.org . Archived from the original on 2015-06-17. Retrieved 2015-06-15 .
^ "SYNPO2 - Synaptopodin-2 - Homo sapiens (Human) - SYNPO2 gene & protein" . uniprot.org .
^ Faul C, Hüttelmaier S, Oh J, Hachet V, Singer RH, Mundel P (May 2005). "Promotion of importin alpha-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3" . The Journal of Cell Biology . 169 (3): 415–24. doi :10.1083/jcb.200411169 . PMC 2171942 . PMID 15883195 .
^ a b c d e f Faul C, Dhume A, Schecter AD, Mundel P (Dec 2007). "Protein kinase A, Ca2+/calmodulin-dependent kinase II, and calcineurin regulate the intracellular trafficking of myopodin between the Z-disc and the nucleus of cardiac myocytes" . Molecular and Cellular Biology . 27 (23): 8215–27. doi :10.1128/MCB.00950-07 . PMC 2169179 . PMID 17923693 .
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