title: The linoleic acid derivative DCP-LA increases membrane surface localization of the α7 ACh receptor in a protein 4.1N-dependent manner.
abstract: In yeast two-hybrid screening, protein 4.1N, a scaffolding protein, was identified as a binding partner of the α7 ACh (acetylcholine) receptor. For rat hippocampal slices, the linoleic acid derivative DCP-LA {8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid} increased the association of the α7 ACh receptor with 4.1N, and the effect was inhibited by GF109203X, an inhibitor of PKC (protein kinase C), although DCP-LA did not induce PKC phosphorylation of 4.1N. For PC-12 cells, the presence of the α7 ACh receptor in the plasma membrane fraction was significantly suppressed by knocking down 4.1N. DCP-LA increased the presence of the α7 ACh receptor in the plasma membrane fraction, and the effect was still inhibited by knocking down 4.1N. In the monitoring of α7 ACh receptor mobilization, DCP-LA enhanced signal intensities for the α7 ACh receptor at the membrane surface in PC-12 cells, which was clearly prevented by knocking down 4.1N. Taken together, the results of the present study show that 4.1N interacts with the α7 ACh receptor and participates in the receptor tethering to the plasma membrane. The results also indicate that DCP-LA increases membrane surface localization of the α7 ACh receptor in a 4.1N-dependent manner under the control of PKC, but without phosphorylating 4.1N.
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Ayako
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Akito
authors.initials: A
authors.lastname: Tanaka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000032:analysis* / Q000378:metabolism*; D014162:Transfection; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C506022:8-(2-(2-pentyl-cyclopropylmethyl)cyclopropyl)octanoic acid; D002210:Caprylates; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D008041:Linoleic Acids; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor