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.
引用
收藏
页码:172 / 181
页数:10
相关论文
共 49 条
[1]   Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD [J].
Beattie, EC ;
Carroll, RC ;
Yu, X ;
Morishita, W ;
Yasuda, H ;
von Zastrow, M ;
Malenka, RC .
NATURE NEUROSCIENCE, 2000, 3 (12) :1291-1300
[2]   A-kinase anchoring proteins take shape [J].
Beene, Darren L. ;
Scott, John D. .
CURRENT OPINION IN CELL BIOLOGY, 2007, 19 (02) :192-198
[3]   AMPA receptor trafficking at excitatory synapses [J].
Bredt, DS ;
Nicoll, RA .
NEURON, 2003, 40 (02) :361-379
[4]   Dynamin-dependent endocytosis of ionotropic glutamate receptors [J].
Carroll, RC ;
Beattie, EC ;
Xia, HH ;
Lüscher, C ;
Altschuler, Y ;
Nicoli, RA ;
Malenka, RC ;
von Zastrow, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :14112-14117
[5]   ASSOCIATION OF PROTEIN-KINASE-A AND PROTEIN-PHOSPHATASE-2B WITH A COMMON ANCHORING PROTEIN [J].
COGHLAN, VM ;
PERRINO, BA ;
HOWARD, M ;
LANGEBERG, LK ;
HICKS, JB ;
GALLATIN, WM ;
SCOTT, JD .
SCIENCE, 1995, 267 (5194) :108-111
[6]   Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex [J].
Colledge, M ;
Dean, RA ;
Scott, GK ;
Langeberg, LK ;
Huganir, RL ;
Scott, JD .
NEURON, 2000, 27 (01) :107-119
[7]   Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression [J].
Colledge, M ;
Snyder, EM ;
Crozier, RA ;
Soderling, JA ;
Jin, YT ;
Langeberg, LK ;
Lu, H ;
Bear, MF ;
Scott, JD .
NEURON, 2003, 40 (03) :595-607
[8]   Receptor trafficking and synaptic plasticity [J].
Collingridge, GL ;
Isaac, JTR ;
Wang, YT .
NATURE REVIEWS NEUROSCIENCE, 2004, 5 (12) :952-962
[9]   Ca2+ signaling requirements for long-term depression in the hippocampus [J].
Cummings, JA ;
Mulkey, RM ;
Nicoll, RA ;
Malenka, RC .
NEURON, 1996, 16 (04) :825-833
[10]   Characterization of the role of microtubule-associated protein 1B in metabotropic glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus [J].
Davidkova, Genoveva ;
Carroll, Reed C. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (48) :13273-13278