title: PICK1 interacts with alpha7 neuronal nicotinic acetylcholine receptors and controls their clustering.
abstract: 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.
authors.affiliation: Department of Neurochemistry, Brain Research Institute, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Kristin
authors.initials: K
authors.lastname: Baer
authors.forename: Thomas
authors.initials: T
authors.lastname: Bürli
authors.forename: Kyung-Hye
authors.initials: KH
authors.lastname: Huh
authors.forename: Andreas
authors.initials: A
authors.lastname: Wiesner
authors.forename: Susanne
authors.initials: S
authors.lastname: Erb-Vögtli
authors.forename: Dubravka
authors.initials: D
authors.lastname: Göckeritz-Dujmovic
authors.forename: Martijn
authors.initials: M
authors.lastname: Moransard
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishimune
authors.forename: Mark I
authors.initials: MI
authors.lastname: Rees
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Henley
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Fritschy
authors.forename: Christian
authors.initials: C
authors.lastname: Fuhrer
mesh_terms: 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
chemical_list: 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