PICK1 interacts with alpha7 neuronal nicotinic acetylcholine receptors and controls their clustering.
Central to synaptic function are protein scaffolds associated with neurotransmitter receptors. Alpha7 neuronal nicotinic acetylcholine receptors (nAChRs) modulate network activity, neuronal survival and cognitive processes in the CNS, but protein scaffolds that interact with these receptors are unknown. Here we show that the PDZ-domain containing protein PICK1 binds to alpha7 nAChRs and plays a role in their clustering. PICK1 interacted with the alpha7 cytoplasmic loop in yeast in a PDZ-dependent way, and the interaction was confirmed in recombinant pull-down experiments and by co-precipitation of native proteins. Some alpha7 and PICK1 clusters were adjacent at the surface of SH-SY5Y cells and GABAergic interneurons in hippocampal cultures. Expression of PICK1 caused decreased alpha7 clustering on the surface of the interneurons in a PDZ-dependent way. These data show that PICK1 negatively regulates surface clustering of alpha7 nAChRs on hippocampal interneurons, which may be important in inhibitory functions of alpha7 in the hippocampus.
Baer
Kristin
K
Department of Neurochemistry, Brain Research Institute, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Bürli
Thomas
T
Huh
Kyung-Hye
KH
Wiesner
Andreas
A
Erb-Vögtli
Susanne
S
Göckeritz-Dujmovic
Dubravka
D
Moransard
Martijn
M
Nishimune
Atsushi
A
Rees
Mark I
MI
Henley
Jeremy M
JM
Fritschy
Jean-Marc
JM
Fuhrer
Christian
C
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D011232:Chemical Precipitation; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D004622:Embryo, Mammalian; D005260:Female; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D020798:Two-Hybrid System Techniques; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002352:Carrier Proteins; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor