Fuhrer
Fakultäten » Medizinische Fakultät » Hirnforschung, Institut für » Prof. Dr. Christian Fuhrer » Fuhrer
Completed research project
| Title / Titel | Role of Src family kinases in formation and stabilization of the neuromuscular synapse | ||
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| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | During neuromuscular synaptogenesis, agrin induces clustering and tyrosine-phosphorylation of acetylcholine receptors (AChRs), by acting through both the receptor tyrosine kinase MuSK and the AChR-associated anchoring protein, rapsyn. We investigate the intracellular steps that follow activation of MuSK, in particular, whether kinases of the Src family are involved. Biochemical experiments using cultured myotubes indicated that a subpopulation of Src and Fyn are bound to the AChR and that they are phosphorylated and activated by agrin. Src/Fyn phosphorylation correlates with AChR clustering, as shown in rapsyn-deficient myotubes, in which AChRs are not clustered and the kinases not activated. In myotubes lacking Src and Fyn, AChRs were aggregated normally by agrin, but the stability of these clusters was strongly reduced. Finally, interfering with Src-family function in electroporated mouse muscle in vivo caused disassembly of adult endplates. Src family kinases acted in concert with lipid rafts. Thus, Src family kinases play a crucial role in stabilization of the postsynapse at the neuromuscular junction. Weitere Informationen |
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| Publications / Publikationen | Willmann, R., Pun, S., Stallmach, L., Sadasivam., G., Santos, A.F., Caroni, P., and Fuhrer, C. 2006. Cholesterol and lipid microdomains stabilize the postsynapse at the neuromuscular junction. EMBO J. 25: 4050-4060.Sadasivam, G., Willmann, R., Lin, S., Erb-Vögtli, S., Kong, X.C., Rüegg. M.A., and Fuhrer, C. 2005. Src-family kinases stabilize the neuromuscular synapse in vivo via protein interactions, phosphorylation, and cytoskeletal linkage of acetylcholine receptors. J. Neurosci. 25:10479-10493.Mittaud, P., Camilleri, A., Willmann, R., Erb-Vögtli, S., Burden, S.J. and Fuhrer, C. (2004). A single pulse of agrin triggers a pathway that acts to cluster acetylcholine receptors. Mol Cell Biol 24: 7841-7854.Willmann, R., and Fuhrer, C. (2002). Neuromuscular synaptogenesis: clustering of acetylcholine receptors revisited. Cell Mol Life Sci. 59: 1296-1316.Mittaud, P., Marangi, P.A., Erb-Vögtli, S. and Fuhrer, C. (2001). Agrin-induced activation of acetylcholine receptor-bound Src family kinases requires rapsyn and correlates with acetylcholine receptor clustering. J Biol Chem 276: 14505-14513.Smith, C.L., Mittaud, P., Prescott, E.D., Fuhrer, C. and Burden, S.J. (2001). Src, Fyn and Yes are not required for neuromuscular synapse formation but are necessary for stabilization of agrin-induced clusters of acetylcholine receptors. J Neurosci 21: 3151-3160.Weitere Informationen | ||
| Keywords / Suchbegriffe | Neurosciences | ||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.neuroscience.uzh.ch/e/groups/fuhrer00.html | ||
| Funding source(s) / Unterstützt durch |
Universität Zürich (position pursuing an academic career), SNF (Personen- und Projektförderung) Swiss Foundation for Research on Muscle Diseases |
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| Duration of Project / Projektdauer | Oct 1998 to Dec 2007 |