Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP.
We identified four PDZ domain-containing proteins, syntenin, PICK1, GRIP, and PSD95, as interactors with the kainate receptor (KAR) subunits GluR5(2b,) GluR5(2c), and GluR6. Of these, we show that both GRIP and PICK1 interactions are required to maintain KAR-mediated synaptic function at mossy fiber-CA3 synapses. In addition, PKC alpha can phosphorylate ct-GluR5(2b) at residues S880 and S886, and PKC activity is required to maintain KAR-mediated synaptic responses. We propose that PICK1 targets PKC alpha to phosphorylate KARs, causing their stabilization at the synapse by an interaction with GRIP. Importantly, this mechanism is not involved in the constitutive recycling of AMPA receptors since blockade of PDZ interactions can simultaneously increase AMPAR- and decrease KAR-mediated synaptic transmission at the same population of synapses.
Hirbec
Hélène
H
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, United Kingdom.
Francis
Joanna C
JC
Lauri
Sari E
SE
Braithwaite
Steven P
SP
Coussen
Françoise
F
Mulle
Christophe
C
Dev
Kumlesh K
KK
Coutinho
Victoria
V
Meyer
Guido
G
Isaac
John T R
JT
Collingridge
Graham L
GL
Henley
Jeremy M
JM
Couthino
Victoria
V
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D053676:Syntenins; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D021122:Protein Subunits; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D011994:Recombinant Proteins; D053676:Syntenins; C501444:DLG4 protein, human; C501447:Dlg4 protein, mouse; C491310:GRIP1 protein, human; C491309:Grip1 protein, mouse; C491308:Grip1 protein, rat; C498298:PICK1 protein, rat; C109621:SDCBP protein, human; C033652:postsynaptic density proteins