cpg2 encodes a brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors

Synaptic plasticity is the rearrangement of neuronal connections that likely underlies learning and memory. It requires the expression of a set of genes essential for the synaptic changes that occur during plasticity, candidate plasticity gene 2 (cpg2) was isolated in a screen for genes that effect synaptic plasticity. In this thesis, I analyze the regulation and function of cpg2 in neurons. I find that cpg2 is a splice-variant of the syne-1 gene that is expressed only in brain regions capable of plasticity and encodes a protein specifically localized to a postsynaptic endocytic zone of excitatory synapses, often in the vicinity of clathrin-coated pits. I further show that, through its C-terminal coiled-coil motifs, CPG2 binds to the actin cytoskeleton and to endophilin B2, a member of a family of proteins involved in membrane trafficking. RNAi-mediated knock-down of CPG2 increased the number of postsynaptic clathrin-coated vesicles, some of which trafficked NMDA receptors, and disrupted the internalization of glutamate receptors. In addition, alterations in its protein levels affected dendritic spine size, supporting a role for CPG2 in regulating membrane trafficking. These data suggest that CPG2 organizes a network of proteins at the postsynaptic endocytic zone critical for glutamate receptor internalization. Due to its unique expression profile and subcellular localization, CPG2 may underlie a novel adaptation of the clathrin-mediated endocytosis pathway that enables the capacity for postsynaptic plasticity in excitatory synapses.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Cottrell, Jeffrey Richard, 1975-

Advisor dc:contributor.advisor

• Elly Nedivi.

• Brain and Cognitive Sciences.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/29372

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/29372