Getu G. Teressa

4th Year Graduate Student

Department: Pharmacological Sciences

Graduate Program: Molecular & Cellular Pharmacology

Advisor: Dr. Joav Prives

Abstract:

Title:  Topogenesis of Postsynaptic Membranes at the Neuromuscular Junction

During neuromuscular junction formation several identified molecular factors are utilized to trigger aggregation of muscle cell surface acetylcholine receptors (AChRs) adjacent to nerve endings. Two extracellular matrix proteins found in synaptic clefts, neural agrin and laminin, are each known to induce clustering of AChRs on the surface of cultured muscle cells by activation of separate transmembrane signaling mechanisms. To characterize the signaling pathways that regulate these aspects of synaptogenesis, we have compared the molecular events that couple agrin and laminin signaling to AChR clustering in C2 muscle cell cultures. Clustering of AChR was induced by exposure of myotubes to soluble agrin, soluble laminin, or substrate-bound laminin. The AChR clusters displayed characteristically different morphologies in each case, suggesting underlying differences in the clustering process or in the endpoint reached. Substrate-coated laminin induces complex branched AChR aggregates more akin to in vivo NMJ compared to the simple ovoid shaped AChR clusters induced by soluble forms of agrin and laminin. However, in all cases AChR clustering was accompanied by, and dependent on activation of the Rho GTPase signaling pathway as well as Focal Adhesion Kinase (FAK). Moreover, AChR clustering is accompanied by enhanced physical association between agrin-and laminin-activated Rho (RhoGTP) and FAK. These data suggest that FAK is a critical integrator of the distinct signals initiated by agrin and laminin possibly upstream of RhoGTPase activation.

Publications:
(MSTP-supported publications indicated with an *)

*Weston, C., Gordon, C., Teressa, G., Hod, E., Ren, X.-D., and Prives, J. (2003). Cooperative regulation by Rac and Rho of agrin-induced acetylcholine receptor clustering in muscle cells. J Biol Chem. 278:6450-5.

*G.Teressa and J.Prives. Focal Adhesion Kinase Integrates Agrin- and Laminin-Induced Acetylcholine Clustering Signals. In preparation.

*G.Teressa and J.Prives. In vitro Experimental Approach to Study Signaling Molecules Involved in a Sequential Postsynaptic Membranes Assembly Akin to NMJ. In preparation.

*Christi A. Weston, Getu Teressa, Benjamin S. Weeks and Joav Prives. Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways. Journal of Cell Science. 120, 868-875.

*Weston, C., Teressa, G., Gordon, C., Weeks, B., and Prives, J. Agrin and Laminin induced acetylcholine receptor clustering via convergent signaling pathways involving Rho GTPases. (Submitted)

Abstracts/Meetings:

Weston, C., Hod, E., Teressa, G., Ren,X.-D., Weeks, B., and Prives, J. (2000). Agrin- and laminin- induced acetylcholine receptor clustering is mediated by the small GTPases Rac, Cdc42, and Rho. 40th American Society for Cell Biology Annual Meeting, San Francisco, CA

Weston, C., Hod, E., Gordon, C., Teressa, G., Ren,X.-D., Weeks, B., and Prives, J.(2001). Mechanism of Rho GTPase-mediated acetylcholine receptor clustering. 41st American Society for Cell Biology Meeting, Washington, DC

Weston, C., Gordon, C., Teressa, G., Scotto-Lavino, E., Weeks, B., and Prives, J. (2002). Rac and Rho cooperatively mediate agrin - induced acetylcholine receptor clustering. 42nd American Society for Cell Biology Meeting, San Francisco, CA.

Weston, C., Teressa, G., Gordon, C., Zarefes, S., and Prives, J. (2003). Localization of Agrin induced acetylcholine receptor clustering is directed by Rac and Rho. 43rd American Society Cell Biology Meeting, San Francisco, CA

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