title: Roles of 14-3-3 and calmodulin binding in subcellular localization and function of the small G-protein Rem2.
abstract: kir/Gem, Rad, Rem and Rem2 comprise the RGK (Rad/Gem/kir) family of Ras-related small G-proteins. Two important functions of RGK proteins are the regulation of the VDCC (voltage-dependent Ca2+ channel) activity and cell-shape remodelling. RGK proteins interact with 14-3-3 and CaM (calmodulin), but their role on RGK protein function is poorly understood. In contrast with the other RGK family members, Rem2 has been reported to bind neither 14-3-3 nor induce membrane extensions. Furthermore, although Rem2 inhibits VDCC activity, it does not prevent cell-surface transport of Ca2+ channels as has been shown for kir/Gem. In the present study, we re-examined the functions of Rem2 and its interaction with 14-3-3 and CaM. We show that Rem2 in fact does interact with 14-3-3 and CaM and induces dendrite-like extensions in COS cells. 14-3-3, together with CaM, regulates the subcellular distribution of Rem2 between the cytoplasm and the nucleus. Rem2 also interacts with the beta-subunits of VDCCs in a GTP-dependent fashion and inhibits Ca2+ channel activity by blocking the alpha-subunit expression at the cell surface. Thus Rem2 shares many previously unrecognized features with the other RGK family members.
authors.affiliation: Epithelial Cell Biology Laboratory, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore. beguinp@imcb.a-star.edu.sg
authors.forename: Pascal
authors.initials: P
authors.lastname: Béguin
authors.forename: Ramasubbu Narayanan
authors.initials: RN
authors.lastname: Mahalakshmi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nagashima
authors.forename: Damian Hwee Kiat
authors.initials: DH
authors.lastname: Cher
authors.forename: Naomitsu
authors.initials: N
authors.lastname: Kuwamura
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Walter
authors.initials: W
authors.lastname: Hunziker
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry* / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001693:Biological Transport, Active; D015220:Calcium Channels / Q000502:physiology; D002147:Calmodulin / Q000737:chemistry* / Q000502:physiology; D002460:Cell Line; D048430:Cell Shape / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D017136:Ion Transport; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D011485:Protein Binding; D020033:Protein Isoforms; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid
chemical_list: D048948:14-3-3 Proteins; D015220:Calcium Channels; D002147:Calmodulin; D020033:Protein Isoforms; D021122:Protein Subunits; D020559:Monomeric GTP-Binding Proteins; C484604:Rem2 protein, rat