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NIDA Proteomics Center
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Investigators
> Pietro De Camilli
Endocytic Mechanisms and
Phosphoinositide Metabolism at Synapses
Pietro De Camilli, Department of Cell Biology and HHMI,
Yale University
Communication between neurons relies heavily upon
the specialized form of membrane traffic responsible for the vesicular release
of neurotransmitters. Membrane traffic is also involved in the control of
synaptic plasticity through modulation of neurotransmitter receptor levels on
the pre- and post-synaptic plasma membranes. These processes have a major impact
in the development of drug addiction. A major focus of my laboratory is the
elucidation of the mechanisms underlying endocytosis in neurons, with emphasis
on the recycling of synaptic vesicle membranes and on the internalization of
neurotransmitter receptors. Progress in this field requires developing a precise
inventory of all the proteins participating in endocytosis as well as a
functional characterization of these proteins using the tools of cell biology,
biophysics and genetics. As studies from our and other labs have shown, the
chemistry of membrane phospholipids also plays an important role in the control
of endocytic traffic. Phosphorylation-dephosphorylation of inositol
phospholipids, in particular, has a key regulatory role at the interface between
membrane dynamics and signaling. Support from the proteomics and lipidomics
cores of the Yale/NIDA Neuroproteomics Center will greatly synergize with
ongoing work of the lab in the following three areas: 1) investigations of the
pathways of phosphoinositide signaling at synapses and their impact on membrane
traffic; 2) studies of of clathrin-mediated endocytosis in neurons; 3)
elucidation of mechanisms that direct post-endocytic protein and membrane
traffic in the endosomal compartment of synapses. It is expected that studies,
which will rely heavily on in vitro cell culture models and on reverse mouse
genetics, will provide the basis for a better understanding of altered signaling
in drug addiction and will reveal new potential targets for the treatment of
addiction.
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