共 49 条
A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors
被引:151
作者:
Bhattacharyya, Samarjit
[1
]
Biou, Virginie
[1
]
Xu, Weifeng
[1
]
Schlueter, Oliver
[1
]
Malenka, Robert C.
[1
]
机构:
[1] Stanford Univ, Sch Med, Nancy Pritzker Lab, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA
基金:
美国国家卫生研究院;
关键词:
LONG-TERM DEPRESSION;
IONOTROPIC GLUTAMATE RECEPTORS;
KINASE-ANCHORING PROTEINS;
EXCITATORY SYNAPSES;
SCAFFOLD PROTEIN;
TRAFFICKING;
ACTIVATION;
PLASTICITY;
AKAP79;
LTD;
D O I:
10.1038/nn.2249
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
The endocytosis of AMPA receptors (AMPARs) underlies several forms of synaptic plasticity, including NMDA receptor (NMDAR)-dependent long-term depression (LTD), but the molecular mechanisms responsible for this trafficking remain unknown. We found that PSD-95, a major postsynaptic density protein, is important for NMDAR-triggered endocytosis of synaptic AMPARs in rat neuron cultures because of its binding to A kinase-anchoring protein 150 (AKAP150), a scaffold for specific protein kinases and phosphatases. Knockdown of PSD-95 with shRNA blocked NMDAR-triggered, but not constitutive or mGluR-triggered, endocytosis of AMPARs. Deletion of PSD-95's Src homology 3 and guanylate kinase-like domains, as well as a point mutation (L460P), both of which inhibit binding of PSD-95 to AKAP150, also blocked NMDAR-triggered AMPAR endocytosis. Furthermore, expression of a mutant AKAP150 that does not bind calcineurin inhibited this NMDAR-triggered trafficking event. Our results suggest that PSD-95's interaction with AKAP150 is critical for NMDAR-triggered AMPAR endocytosis and LTD, possibly because these scaffolds position calcineurin in the appropriate subsynaptic domain.
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页码:172 / 181
页数:10
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