Getu
G. Teressa
4th
Year Graduate Student
Department: Pharmacological Sciences
Graduate
Program: Molecular & Cellular
Pharmacology
Advisor: Dr. Joav Prives
Abstract:
Title:
Assembly of Postsynaptic Membranes at the Neuromuscular
Junction
Getu
Teressa1, 2 and Joav Prives1
1Department
of Pharmacological Sciences, Stony Brook University, Stony Brook,
NY 11794
2 Medical Scientist Training Program, Stony Brook University, Stony
Brook, NY 11794, USA
A key feature of postsynaptic specialization at the neuromuscular
junction (NMJ) is the accumulation of high densities of acetylcholine
receptors (AChR) immediately under the nerve ending. But the molecular
mechanisms responsible for this phenomenon are poorly understood.
Our study investigated the role of the Focal Adhesion Kinase (FAK)
in mediating the formation of AChR aggregates in response to the signaling
molecules agrin and laminin. Our findings show that clustering of
AChR on the surface of skeletal muscle cells by either agrin or laminin
is associated with increased phosphorylation of FAK at tyrosine residues.
Moreover, FAK inhibition by either siRNA induced FAK knockdown, or
of a pharmacological blocker of FAK catalytic activity abolishes AChR
cluster formation. Our results indicate that FAK utilizes both kinase-dependent
and –independent mechanisms in coupling agrin and laminin stimulation
to AChR aggregation. In addition, FAK forms functional complexes with
Rho as well as surface AChR, and colocalizes with AChR aggregates
both in cultured myotubes and in vivo at intact mouse diaphragm
NMJs.
Publications:
(MSTP-supported publications indicated with an *)
Getu Teressa and Joav Prives. Cell culture-based
analysis of postsynaptic membrane assembly in muscle cells. Biological
Procedure Onine. Accepted.
Getu
Teressa and Joav Prives. Integration by Focal Adhesion Kinase
of Signaling Pathways that Regulate Neuromuscular Synapse Formation.
Submitted.
*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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