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Ca 2+ /calmodulin binding to PSD ‐95 mediates homeostatic synaptic scaling down
Author(s) -
Chowdhury Dhrubajyoti,
Turner Matthew,
Patriarchi Tommaso,
Hergarden Anne C,
Anderson David,
Zhang Yonghong,
Sun Junqing,
Chen ChaoYin,
Ames James B,
Hell Johannes W
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695829
Subject(s) - library science , computer science
Postsynaptic density protein‐95 ( PSD ‐95) localizes AMPA ‐type glutamate receptors ( AMPAR s) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPAR s during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca 2+ influx, Ca 2+ /calmodulin (Ca 2+ /CaM) binding to the N‐terminus of PSD ‐95 mediates postsynaptic loss of PSD ‐95 and AMPAR s during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD‐95 N‐terminus as important for binding to Ca 2+ /CaM by interacting with R126 on CaM. Mutating E17 to R prevented homeostatic scaling down in primary hippocampal neurons, which is rescued via charge inversion by ectopic expression of Ca M R 126E , as determined by analysis of miniature excitatory postsynaptic currents. Accordingly, increased binding of Ca 2+ /CaM to PSD ‐95 induced by a chronic increase in Ca 2+ influx is a critical molecular event in homeostatic downscaling of glutamatergic synaptic transmission.