Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF.
A recently described form of synaptic plasticity results in dynamic changes in the calcium permeability of synaptic AMPA receptors. Since the AMPA receptor GluR2 subunit confers calcium permeability, this plasticity is thought to occur through the dynamic exchange of synaptic GluR2-lacking and GluR2-containing receptors. To investigate the molecular mechanisms underlying this calcium-permeable AMPA receptor plasticity (CARP), we examined whether AMPA receptor exchange was mediated by subunit-specific protein-protein interactions. We found that two GluR2-interacting proteins, the PDZ domain-containing Protein interacting with C kinase (PICK1) and N-ethylmaleimide sensitive fusion protein (NSF), are specifically required for CARP. Furthermore, PICK1, but not NSF, regulates the formation of extrasynaptic plasma membrane pools of GluR2-containing receptors that may be laterally mobilized into synapses during CARP. These results demonstrate that PICK1 and NSF dynamically regulate the synaptic delivery of GluR2-containing receptors during CARP and thus regulate the calcium permeability of AMPA receptors at excitatory synapses.
Gardner
Stephanie M
SM
Department of Neuroscience, Johns Hopkins University, School of Medicine, Howard Hughes Medical Institute, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
Takamiya
Kogo
K
Xia
Jun
J
Suh
Jun-Gyo
JG
Johnson
Richard
R
Yu
Sandy
S
Huganir
Richard L
RL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D003598:Cytoskeletal Proteins; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D052066:N-Ethylmaleimide-Sensitive Proteins; D009473:Neuronal Plasticity / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011940:Receptor Aggregation / Q000502:physiology; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D015220:Calcium Channels; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; C091822:Prkcabp protein, mouse; D021122:Protein Subunits; D018091:Receptors, AMPA; D033921:Vesicular Transport Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins; C498733:Nsf protein, mouse; C498737:Nsf protein, rat; D034281:Dynamins; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium