Synapses represent specialized intercellular junctions at which a presynaptic neuron secretes neurotransmitters that excite the postsynaptic neuron. Presynaptic neurons secrete neurotransmitters by calcium-regulated exocytosis only at the synaptic cleft, while postsynaptic neurons recognize the transmitters via receptors that are clustered in the plasma membrane facing the synaptic cleft. Our laboratory is interested in understanding how presynaptic neurons recognize a postsynaptic cell to form a synapse, how synapses are organized via cell-adhesion molecules, and how neurotransmitters are released at a synapse. We pursue these questions by a combination of genetic, biochemical, and cell biological methods. One of our major interests regards the functions of neurexins, a class of polymorphic neuron-specific cell surface proteins that may function as cell-adhesion molecules at the synapse. Neurexins serve as receptors for alpha-latrotoxin, which triggers synaptic vesicle exocytosis, and bind intracellularly to a number of PDZ-domain proteins. In addition, we are studying the mechanism of membrane fusion at the synpapse, and its regulation by calcium. Here we have discovered a number of proteins containing C2-domains, universal calcium-binding domains, that regulate the amount of exocytotic fusion, for example synaptotagmin, munc13, and RIM. The long-term goal of these studies is to achieve a molecular description of presynaptic function as a prerequisite of understanding how synapses compute information in the brain.
RESEARCH INTERESTS
Neuroscience
Cell Biology
Alzheimer's Disease
Parkinson's Disease
RECENT PUBLICATIONS
Fernandez-Chacon, R.F., Wolfel, M., Nishimune, H., Tabares, L., Schmitz, F., Castellano-Mu?oz, M., Rosenmund, C., Montesinos, M.L., Sanes, J.R., Schneggenburger, R., and Sudhof, T.C., "The Synaptic Vesicle Protein CSP Prevents Presynaptic Degeneration." Neuron , 237-251, 42 Spring 2004
Fernandez-Chacon, R.F., Wolfel, M., Nishimune, H., Tabares, L., Schmitz, F., Castellano-Mu?oz, M., Rosenmund, C., Montesinos, M.L., Sanes, J.R., Schneggenburger, R., and Sudhof, T.C., "The Synaptic Vesicle Protein CSP Prevents Presynaptic Degeneration." Neuron, 42:237-251, Spring 2004
Lonart, G., Schoch, S., Kaeser, P.S., Larkin, C.J., Sudhof, T.C., and Linden, D.J., "Phosphorylation of RIM1 by PKA Triggers Presynaptic LTP at Cerebellar Parallel Fiber Synapses." Cell, 115:49-60, Winter 2003
Han, W., Rhee, J.S., Maximov, A., Lao, Y., Mashimo, T., Rosenmund, C., and Sudhof, T,C., "N-glycosylation is essential for vesicular targeting of synaptotagmin 1" Neuron, 41:85-99, Spring 2004
Missler, M., Zhang, W., Rohlmann, A., Kattenstroth, G., Hammer, R.E., Gottmann, K., and Sudhof, T.C., "-Neurexins Couple Ca2+-Channels to Synaptic Vesicle Exocytosis" Nature, 423:939-948, Summer 2003
Cao, X., and Sudhof, T.C., "Dissection of APP-dependent transcriptional transactivation." J. Biol. Chemistry, 279:24601-24611, Summer 2004
SIGNIFICANT PUBLICATIONS
Schoch, S., Castillo, P.E., Jo, T., Mukherjee, K., Geppert, M., Wang, Y., Schmitz, F., Malenka, R.C., and Sudhof, T.C., "RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone." Nature, 415:321-326, Spring 2002
Fernandez-Chacon, R., Konigstorffer, Gerber, S.H., Garcia, J., Matos, M.F., Stevens, C.F., Brose, N., Rizo, J. Rosenmund, C., and Sudhof, T.C., "Synaptotagmin I functions as a Ca2+-regulator of release probability." Nature, 410:41-49, Spring 2001
Hata, Y., Slaughter, C.A., and Sudhof, T.C., "Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin" Nature, 366:347-351, Fall 1993
Geppert, M., Goda, Y., Hammer, R.E., Li, C., Rosahl, T.W., Stevens, C.F., and Sudhof, T.C, "Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse." Cell, 79:717-727, Summer 1994
Ushkaryov, Y.A., Petrenko, A.G., Geppert, M. and Sudhof, T.C., "Neurexins: Synaptic cell surface proteins related to the α-latrotoxin receptor and laminin." Scienc e, 257:50-56, Summer 1992
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