Phosphorylation of Delta2 Glutamate Receptors at Serine 945 is Not Required for Cerebellar Long-term Depression
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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, theδ2 glutamate receptor (GluRδ2), which is predominantly expressed at PF-Purkinje cell synapses, is indispensable for the induction of LTD; however, the mechanisms by which GluRδ2 regulates LTD and its relationship with PKC activation remain elusive. Interestingly, GluRδ2 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 GluRδ2 in a phosphorylation-dependent manner on Ser945. Here, using a Sindbis-based virus expression approach, we show that a mutant GluRδ2, 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 GluRδ2, the phosphorylation-disrupted GluRδ2 successfully rescued abrogated LTD in <i>GluRδ2</i>-null Purkinje cells. These results indicate that Ser945, a major PKC phosphorylation site of of GluRδ2, may not play a crucial role in induction of LTD in the cerebellum.
- Keio J. Med.
Keio J. Med. 57(2), 105-110, 2008-06-01
The Keio Journal of Medicine