Protein interacting with C kinase 1 (PICK1) and GluR2 are associated with presynaptic plasma membrane and vesicles in hippocampal excitatory synapses.
AMPA receptors have been identified in different populations of presynaptic terminals and found to be involved in the modulation of neurotransmitter release. The mechanisms that govern the expression of presynaptic AMPA receptors are not known. One possibility is that pre- and postsynaptic AMPA receptors are regulated according to the same principles. To address this hypothesis we investigated whether protein interacting with C kinase 1 (PICK1), known to interact with AMPA receptors postsynaptically, also is expressed presynaptically, together with AMPA receptors. Subfractionation and high-resolution immunogold analyses of the rat hippocampus revealed that GluR2 and PICK1 are enriched postsynaptically, but also in presynaptic membrane compartments, including the active zone and vesicular membranes. PICK1 and GluR2 are associated with the same vesicles, which are immunopositive also for synaptophysin and vesicle-associated membrane protein 2. Based on what is known about the function of PICK1 postsynaptically, the present data suggest that PICK1 is involved in the regulation of presynaptic AMPA receptor trafficking and in determining the size of the AMPA receptor pool that modulates presynaptic glutamate release.
Haglerød
C
C
Institute of Basic Medical Sciences, Department of Anatomy, and Centre for Molecular Biology and Neuroscience, University of Oslo, P.O. Box 1105 Blindern, 0317 Oslo, Norway.
Kapic
A
A
Boulland
J-L
JL
Hussain
S
S
Holen
T
T
Skare
O
O
Laake
P
P
Ottersen
O P
OP
Haug
F-M S
FM
Davanger
S
S
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006367:HeLa Cells; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009687:Nuclear Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D018091:Receptors, AMPA; D016708:Synaptophysin; C494706:Vamp2 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; C104722:glutamate receptor ionotropic, AMPA 2