@article{9353161b74354630a139c7974421a6f3,
title = "Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression",
abstract = "Cerebellar long-term depression (LTD) is a major form of synaptic plasticity that is thought to be critical for certain types of motor learning. Phosphorylation of the AMPA receptor subunit GluR2 on serine-880 as well as interaction of GluR2 with PICK1 have been suggested to contribute to the endocytic removal of postsynaptic AMPA receptors during LTD. Here, we show that targeted mutation of PICK1, the GluR2 C-terminal PDZ ligand, or the GluR2 PKC phosphorylation site eliminates cerebellar LTD in mice. LTD can be rescued in cerebellar cultures from mice lacking PICK1 by transfection of wild-type PICK1 but not by a PDZ mutant or a BAR domain mutant deficient in lipid binding, indicating the importance of these domains in PICK1 function. These results demonstrate that PICK1-GluR2 PDZ-based interactions and GluR2 phosphorylation are required for LTD expression in the cerebellum.",
author = "Steinberg, {Jordan P.} and Kogo Takamiya and Ying Shen and Jun Xia and Rubio, {Maria E.} and Sandy Yu and Wenying Jin and Thomas, {Gareth M.} and Linden, {David J.} and Huganir, {Richard L.}",
note = "Funding Information: We thank R. Bock for superior technical assistance with cerebellar culture preparation, C. Yu for assistance with mouse-line maintenance and histologic analysis, R. Johnson for technical assistance with cDNA mutagenesis, M. Coulter for antibody preparation, N. Ramanan for assistance with Golgi staining and microscope image acquisition, and D.T. Lin for assistance with image processing and quantification. This work was supported by research grants from the National Institutes of Health NS 36715, the Robert Packard Center for ALS Research, and the Muscular Dystrophy Association's Wings Over Wall Street (to R.L.H); by PHS MH51106 and the Develbiss Fund (to D.J.L.); and by Research Grants Council of Hong Kong (to J.X.). Under a licensing agreement between Upstate Group, Inc., and The Johns Hopkins University, R.L.H. is entitled to a share of royalties received by the University on sales of products described in this article. R.L.H. is a paid consultant to Upstate Group, Inc. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies. ",
year = "2006",
month = mar,
day = "16",
doi = "10.1016/j.neuron.2006.02.025",
language = "English (US)",
volume = "49",
pages = "845--860",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}