Cottrell JR, Borok E, Horvath TL, Nedivi E.
CPG2: a brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors.
Neuron. 2004 Nov 18;44(4):677-90.
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This is a very nice paper! Using a thorough, systematic approach, the authors found that cpg2, a gene they previously identified to be upregulated by kainic acid-induced seizures, encodes a protein localized specifically to an endocytic zone within spines distinct from the postsynaptic density. Modulation of CPG2 protein levels can affect the spine size in cultured neurons. Reduction of CPG2 by RNAi decreases constitutive or activity-induced internalization of NMDARs and AMPARs, indicating that CPG2 is important for glutamate receptor internalization. As receptor internalization has been proposed as a mechanism for LTD, it will be interesting to see whether cpg2 KO mice would have an affected LTD induction (though the mice may exhibit more complex phenotypes). And it is not yet clear how CPG2 regulates receptor internalization. Whether CPG2 is a key component of a specialized mechanism for glutamate receptor internalization will require further experimentation.