Synaptic transmission is the major cellular process used for intercellular communication between neurons in the brain. In the last several years many of the proteins important in mediating neurotransmitter release have been identified and functional studies have led to a series of proposals for the biochemical pathway of vesicle docking, activation and release. In spite of this progress, many critical events in membrane trafficking within the nerve terminal are not understood and the roles of many proteins remain to be determined. Two recently identified mammalian proteins, rsec6 and rsec8, share sequence homology =with yeast genes important for secretion. This proposal will investigate the potential roles of these molecules in presynaptic transmitter release. We will test the specific hypothesis that the rsec6 and rsec8 molecules function in conjunction with a low-molecular weight GTPase, or Rab protein, to regulate early aspects of vesicle docking. Further, we propose to study the localization of the rsec6 and rsec8 molecules and to characterize their biochemical interactions with other components of the secretory pathway. These studies are expected to further elucidate the molecular mechanisms of neurotransmitter secretion at the synapse. the molecules involved in transmitter release are likely targets for diseases that lead to neurologic and psychiatric disorders of athe nervous system. In addition, understanding biochemical pathway leading to transmitter release may some day allow the rational design of therapeutic compounds useful in treating diseases of the nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH048108-10
Application #
6347621
Study Section
Project Start
2000-09-01
Project End
2001-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
10
Fiscal Year
2000
Total Cost
$154,408
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Murthy, Mala; Garza, Dan; Scheller, Richard H et al. (2003) Mutations in the exocyst component Sec5 disrupt neuronal membrane traffic, but neurotransmitter release persists. Neuron 37:433-47
Gorska-Andrzejak, J; Stowers, R S; Borycz, J et al. (2003) Mitochondria are redistributed in Drosophila photoreceptors lacking milton, a kinesin-associated protein. J Comp Neurol 463:372-88
Finley, Michael F A; Scheller, Richard H; Madison, Daniel V (2003) SNAP-25 Ser187 does not mediate phorbol ester enhancement of hippocampal synaptic transmission. Neuropharmacology 45:857-62
Deisseroth, Karl; Mermelstein, Paul G; Xia, Houhui et al. (2003) Signaling from synapse to nucleus: the logic behind the mechanisms. Curr Opin Neurobiol 13:354-65
Waters, Jack; Smith, Stephen J (2002) Vesicle pool partitioning influences presynaptic diversity and weighting in rat hippocampal synapses. J Physiol 541:811-23
Horrigan, Frank T; Aldrich, Richard W (2002) Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels. J Gen Physiol 120:267-305
Stowers, R Steven; Megeath, Laura J; Gorska-Andrzejak, Jolanta et al. (2002) Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 36:1063-77
Hopf, F Woodward; Waters, Jack; Mehta, Samar et al. (2002) Stability and plasticity of developing synapses in hippocampal neuronal cultures. J Neurosci 22:775-81
Montgomery, Johanna M; Madison, Daniel V (2002) State-dependent heterogeneity in synaptic depression between pyramidal cell pairs. Neuron 33:765-77
Finley, Michael F A; Patel, Sejal M; Madison, Daniel V et al. (2002) The core membrane fusion complex governs the probability of synaptic vesicle fusion but not transmitter release kinetics. J Neurosci 22:1266-72

Showing the most recent 10 out of 81 publications