Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression.
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.
Nakagami
Ryoichi
R
Department of Physiology, School of Medicine, Keio University, Department of Psychiatry, University of Tokyo, Tokyo, Japan.
Kohda
Kazuhisa
K
Kakegawa
Wataru
W
Kondo
Tetsuro
T
Kato
Nobumasa
N
Yuzaki
Michisuke
M
D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D004594:Electrophysiology; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism; D017470:Receptors, Glutamate / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2; D010768:Phosphoserine