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Title: Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression. Author: Nakagami R, Kohda K, Kakegawa W, Kondo T, Kato N, Yuzaki M. Journal: Keio J Med; 2008 Jun; 57(2):105-10. PubMed ID: 18677091. Abstract: Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell synapses is thought to regulate motor learning and memory formation in the cerebellum. Neuronal activity-evoked protein kinase C (PKC) activation is required for the induction of LTD. In addition, the delta2 glutamate receptor (GluRdelta2), which is predominantly expressed at PF-Purkinje cell synapses, is indispensable for the induction of LTD; however, the mechanisms by which GluRdelta2 regulates LTD and its relationship with PKC activation remain elusive. Interestingly, GluRdelta2 is phosphorylated by PKC on serine 945 (Ser945) near its C-terminus and a postsynaptic protein S-SCAM, which could potentially regulate glutamate receptor trafficking and synaptic plasticity, binds to the extreme C-terminus of GluRdelta2 in a phosphorylation-dependent manner on Ser945. Here, using a Sindbis-based virus expression approach, we show that a mutant GluRdelta2, in which alanine replaced Ser945 and did not undergo PKC phosphorylation, was normally localized at the postsynaptic sites of PF-Purkinje cell synapses. In addition, like wild-type GluRdelta2, the phosphorylation-disrupted GluRdelta2 successfully rescued abrogated LTD in GluRdelta2-null Purkinje cells. These results indicate that Ser945, a major PKC phosphorylation site of of GluRdelta2, may not play a crucial role in induction of LTD in the cerebellum.[Abstract] [Full Text] [Related] [New Search]