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| The EMBO Journal
(2000) 19, 2765–2774, doi:10.1093/emboj/19.12.2765 |
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| Disruption of AMPA receptor GluR2 clusters following long-term depression induction in cerebellar Purkinje neurons |
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| Shinji Matsuda, Thomas Launey, Sumiko Mikawa and Hirokazu Hirai |
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Laboratory for Memory and Learning, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan To whom correspondence should be addressed Hirokazu Hirai, hirai@postman.riken.go.jp Received 21 February 2000; Revised 12 April 2000; Accepted 17 April 2000. |
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| Abstract |
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| Cerebellar long-term depression (LTD) is thought to play an important role in certain types of motor learning. However, the molecular mechanisms underlying this event have not been clarified. Here, using cultured Purkinje cells, we show that stimulations inducing cerebellar LTD cause phosphorylation of Ser880 in the intracellular C-terminal domain of the AMPA receptor subunit GluR2. This phosphorylation is accompanied by both a reduction in the affinity of GluR2 to glutamate receptor interacting protein (GRIP), a molecule known to be critical for AMPA receptor clustering, and a significant disruption of postsynaptic GluR2 clusters. Moreover, GluR2 protein released from GRIP is shown to be internalized. These results suggest that the dissociation of postsynaptic GluR2 clusters and subsequent internalization of the receptor protein, initiated by the phosphorylation of Ser880, are the mechanisms underlying the induction of cerebellar LTD. |
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| Keywords: AMPA receptor, cluster, GluR2, LTD, Purkinje cell |
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