SYNPO2 explained

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). 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.

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. 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. The nuclear localization of myopodin is sensitive to Importin 13, which directly binds myopodin and facilitates its translocation.^[2] Importin binding and nuclear import of myopodin appears to be mediated by serine/threonine phosphorylation-dependent binding of myopodin to 14-3-3 beta^[6] 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.^[7] 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.^[7]

Interactions

Myopodin interacts with:

• 14-3-3 beta,^[7]
• Actin, alpha, cardiac muscle 1,
• Actinin, alpha 2,
• Calcineurin,^[7]
• CaMKII,^[7]
• Importin 13,^[2] and
• Protein kinase A.^[7]

Further reading

• Houlgatte R, Mariage-Samson R, Duprat S, Tessier A, Bentolila S, Lamy B, Auffray C . The Genexpress Index: a resource for gene discovery and the genic map of the human genome . Genome Research . 5 . 3 . 272–304 . Oct 1995 . 8593614 . 10.1101/gr.5.3.272 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . Nov 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . Mar 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Reports . 1 . 3 . 287–92 . Sep 2000 . 11256614 . 1083732 . 10.1093/embo-reports/kvd058 .
• Van Impe K, De Corte V, Eichinger L, Bruyneel E, Mareel M, Vandekerckhove J, Gettemans J . The Nucleo-cytoplasmic actin-binding protein CapG lacks a nuclear export sequence present in structurally related proteins . The Journal of Biological Chemistry . 278 . 20 . 17945–52 . May 2003 . 12637565 . 10.1074/jbc.M209946200 . free .
• Sanchez-Carbayo M, Schwarz K, Charytonowicz E, Cordon-Cardo C, Mundel P . Tumor suppressor role for myopodin in bladder cancer: loss of nuclear expression of myopodin is cell-cycle dependent and predicts clinical outcome . Oncogene . 22 . 34 . 5298–305 . Aug 2003 . 12917631 . 10.1038/sj.onc.1206616 . free .
• Jing L, Liu L, Yu YP, Dhir R, Acquafondada M, Landsittel D, Cieply K, Wells A, Luo JH . Expression of myopodin induces suppression of tumor growth and metastasis . The American Journal of Pathology . 164 . 5 . 1799–806 . May 2004 . 15111326 . 1615646 . 10.1016/S0002-9440(10)63738-8 .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . Oct 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S . The LIFEdb database in 2006 . Nucleic Acids Research . 34 . Database issue . D415–8 . Jan 2006 . 16381901 . 1347501 . 10.1093/nar/gkj139 .

Notes and References

1. Weins A, Schwarz K, Faul C, Barisoni L, Linke WA, Mundel P . Differentiation- and stress-dependent nuclear cytoplasmic redistribution of myopodin, a novel actin-bundling protein . The Journal of Cell Biology . 155 . 3 . 393–404 . Oct 2001 . 11673475 . 2150840 . 10.1083/jcb.200012039 .
2. Liang J, Ke G, You W, Peng Z, Lan J, Kalesse M, Tartakoff AM, Kaplan F, Tao T . Interaction between importin 13 and myopodin suggests a nuclear import pathway for myopodin . Molecular and Cellular Biochemistry . 307 . 1–2 . 93–100 . Jan 2008 . 17828378 . 10.1007/s11010-007-9588-1 . 19273082 .
3. Web site: Entrez Gene: SYNPO2 synaptopodin 2.
4. Web site: Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information. Joon-Sub Chung. heartproteome.org. 2015-06-15. 2015-06-17. https://web.archive.org/web/20150617124610/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q9UMS6. dead.
5. Web site: SYNPO2 - Synaptopodin-2 - Homo sapiens (Human) - SYNPO2 gene & protein. uniprot.org.
6. Faul C, Hüttelmaier S, Oh J, Hachet V, Singer RH, Mundel P . 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 . May 2005 . 15883195 . 2171942 . 10.1083/jcb.200411169 .
7. Faul C, Dhume A, Schecter AD, Mundel P . 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 . Dec 2007 . 17923693 . 2169179 . 10.1128/MCB.00950-07 .