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Endocrinology, doi:10.1210/en.2008-0274
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Endocrinology Vol. 149, No. 12 6006-6017
Copyright © 2008 by The Endocrine Society

Expression of Neurexin, Neuroligin, and Their Cytoplasmic Binding Partners in the Pancreatic β-Cells and the Involvement of Neuroligin in Insulin Secretion

Arthur T. Suckow, Davide Comoletti, Megan A. Waldrop, Merrie Mosedale, Sonya Egodage, Palmer Taylor and Steven D. Chessler

Department of Medicine (A.T.S., M.A.W., M.M., S.E., S.D.C.), Biomedical Sciences Graduate Program (A.T.S., M.M.), and Skaggs School of Pharmacy and Pharmaceutical Sciences (D.C., P.T.), University of California, San Diego, La Jolla, California 92093

Address all correspondence and requests for reprints to: Steven D. Chessler, University of California, San Diego, Leichtag Biomedical Research Building, 9500 Gilman Drive MC 0726, La Jolla, California 92093-0726. E-mail: schessler{at}ucsd.edu.

The composition of the β-cell exocytic machinery is very similar to that of neuronal synapses, and the developmental pathway of β-cells and neurons substantially overlap. β-Cells secrete {gamma}-aminobutyric acid and express proteins that, in the brain, are specific markers of inhibitory synapses. Recently, neuronal coculture experiments have identified three families of synaptic cell-surface molecules (neurexins, neuroligins, and SynCAM) that drive synapse formation in vitro and that control the differentiation of nascent synapses into either excitatory or inhibitory fully mature nerve terminals. The inhibitory synapse-like character of the β-cells led us to hypothesize that members of these families of synapse-inducing adhesion molecules would be expressed in β-cells and that the pattern of expression would resemble that associated with neuronal inhibitory synaptogenesis. Here, we describe β-cell expression of the neuroligins, neurexins, and SynCAM, and show that neuroligin expression affects insulin secretion in INS-1 β-cells and rat islet cells. Our findings demonstrate that neuroligins and neurexins are expressed outside the central nervous system and help confer an inhibitory synaptic-like phenotype onto the β-cell surface. Analogous to their role in synaptic neurotransmission, neurexin-neuroligin interactions may play a role in the formation of the submembrane insulin secretory apparatus.







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Copyright © 2008 by The Endocrine Society