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Frédérique Varoqueaux"Role of Neuroligins in Synapse Formation and Function"

Abstract :

Functional alterations of synaptic connections in the central nervous system are underlying numerous psychiatric, neurologic and motor disorders, and are accompanied by first- or second-order structural changes.
Synaptic transmission rely on proper neurotransmitter release at the presynapse, and on the correct assembly of specific adhesion, scaffold, receptor, and signalling proteins both at the pre- and the post-synapse. Neuroligins are postsynaptic adhesion proteins in which mutations have been causally linked to cases of autism. While Neuroligins are thought to be crucial for synapse function, only limited analysis has been performed to determine the exact nature of alterations induced by their absence in a given neuronal network. I will report on the recent identification of interaction partners for Neuroligin2, an isoform present at all inhibitory synapses in vivo. Also, I will summarize the nature of synaptic reorganizations we have identified through an integrative biochemical, morphological and functional approach in specific areas of the Neuroligin2-deficient mouse.

Selected publications

Pivot-Pajot C, Varoqueaux F, de Saint Basile G, Bourgoin SG.
Munc13-4 regulates granule secretion in human neutrophils.
J Immunol. 2008 May 15;180(10):6786-97.
Zikich D, Mezer A, Varoqueaux F, Sheinin A, Junge HJ, Nachliel E, Melamed R, Brose N, Gutman M, Ashery U.
Vesicle priming and recruitment by ubMunc13-2 are differentially regulated by calcium and calmodulin.
J Neurosci. 2008 Feb 20;28(8):1949-60
Jamain S, Radyushkin K, Hammerschmidt K, Granon S, Boretius S, Varoqueaux F, Ramanantsoa N, Gallego J, Ronnenberg A, Winter D, Frahm J, Fischer J, Bourgeron T, Ehrenreich H, Brose N.
Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism.
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1710-5.
Jockusch WJ, Speidel D, Sigler A, Sørensen JB, Varoqueaux F, Rhee JS, Brose N.
CAPS-1 and CAPS-2 are essential synaptic vesicle priming proteins.
Cell. 2007 Nov 16;131(4):796-808
Wegmeyer H, Egea J, Rabe N, Gezelius H, Filosa A, Enjin A, Varoqueaux F, Deininger K, Schnütgen F, Brose N, Klein R, Kullander K, Betz A.
EphA4-dependent axon guidance is mediated by the RacGAP alpha2-chimaerin.
Neuron. 2007 Sep 6;55(5):756-67