David Bredt, MD/PhD
Molecular Basis of Postsynaptic Organization
| email |
bredt@phy.ucsf.edu |
| phone |
415-476-6310
415-476-6734 |
| office location |
physical address:
N-272F, Genentech Hall 600 16th Street
Mission Bay Campus
mailing address:
UCSF
Genentech Hall
600 16th Street
Box 2140
San Francisco, CA 94143-2140
For internal campus mail: Box 2140 |
other
websites |
PIBS website
Biomedical Sciences
Graduate Program | Research Summary | Current Projects
Lab Personnel | Publications |
|
Neurons take in vast amounts of chemical information at their postsynaptic termini, and a central question is how this complex array of inputs is correctly processed. Our lab focuses on postsynaptic processing at excitatory synapses in brain. Transmission at these excitatory synapses is mediated primarily by glutamate acting on two classes of ligand gated ion channels: AMPA receptors and NMDA receptors. The AMPA receptors are involved in moment-to-moment signaling, whereas NMDA receptors play an important role in initiating synaptic plasticity.
A key breakthrough in understanding mechanisms for synapse assembly came from the discovery that proteins containing PDZ motifs play central roles in scaffolding receptors and signaling elements. The prototypical PDZ protein, PSD-95, associates with NMDA receptors and a downstream effector neuronal nitric oxide synthase. By bridging the NMDA receptor to nNOS, PSD-95 functions as a scaffold to enhance activation of calmodulin-dependent nNOS activity by Ca2+ influx through the NMDA receptor. In addition to mediating synapse assembly through its PDZ domains, PSD-95 participates in synaptic plasticity through its regulatory domains. We are using cellular, structural and physiological approaches to understand how the regulatory domains of PSD-95, which include an SH3 domain, a guanylate kinase domain, and sites for N-terminal palmitoylation mediate synaptic plasticity.
Whereas numerous cytoskeletal elements bind to glutamate receptors, the first transmembrane protein found to interact with glutamate receptors is stargazin. Working together with Dr. Roger Nicoll's group, we found that stargazer mutant mice lack synaptic AMPA responses due to a block in AMPA receptor trafficking. Stargazin is a tetraspanin, a protein with four transmembrane domains that links AMPA receptors to PDZ proteins at the synapse. Our current work focuses on how stargazin promotes delivery of AMPA receptors to the plasma membrane and on how stargazin regulates the synaptic cycling of AMPA receptors that underlies synaptic plasticity.
See above.
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Only current lab members are listed below. Click on the icon to open a list of former lab members. |
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Bonnie Firestein |
Postdoctoral Fellow 7/95-Present |
Ph.D. UC San Diego |
Nitric oxide and neuronal development |
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Karen Christopherson |
Graduate Student 9/95-Present |
B.S. UC Berkeley |
NOS/NMDAR protein complex |
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Sarah Craven |
Graduate Student 9/96-Present |
B.A. Boston University |
PSD-95 localization |
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Aaron McGee |
Graduate Student 9/96-Present |
B.A. Univ. of Colorado |
Cellular mechs of synaptic plasticity |
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Kiwon Jo |
Postdoctoral Fellow 8/97-Present |
Ph.D. Univ. of North Carolina |
FSH muscular dystrophy |
|
Alaa El-Din El Husseini |
Postdoctoral Fellow 8/97-Present |
Ph.D. Univ. of British Columbia, Vancouver |
Mechanisms for postsynaptic targeting |
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Hidemi Misawa |
Postdoctoral Fellow 4/98-Present |
Ph.D. Kyoto University |
Postsynaptic organization |
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Srikanth Dakoji |
Postdoctoral Fellow 11/98-Present |
Ph.D. Univ. of Minnesota |
Palmitoylation and protein targeting |
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Dane Chetkovich |
Postdoctoral Fellow 11/98-Present |
M.D., Ph.D. Baylor College of Medicine |
Postsynaptic development |
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Robert Bunn |
Postdoctoral Fellow 2/1/99-Present |
Ph.D. Louisiana State Univ. |
ALP & muscular dystrophy |
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(责任编辑：泉水) |
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