title: Calexcitin: a signaling protein that binds calcium and GTP, inhibits potassium channels, and enhances membrane excitability.
abstract: A previously uncharacterized 22-kDa Ca(2+)-binding protein that also binds guanosine nucleotides was characterized, cloned, and analyzed by electrophysiological techniques. The cloned protein, calexcitin, contains two EF-hands and also has homology with GTP-binding proteins in the ADP ribosylation factor family. In addition to binding two molecules of Ca2+, calexcitin bound GTP and possessed GTPase activity. Calexictin is also a high affinity substrate for protein kinase C. Application of calexcitin to the inner surface of inside-out patches of human fibroblast membranes, in the presence of Ca2+ and the absence of endogenous Ca2+/calmodulin kinase type II or protein kinase C activity, reduced the mean open time and mean open probability of 115 +/- 6 pS K+ channels. Calexcitin thus appears to directly regulate K+ channels. When microinjected into molluscan neurons or rabbit cerebellar Purkinje cell dendrites, calexcitin was highly effective in enhancing membrane excitability. Because calexcitin translocates to the cell membrane after phosphorylation, calexcitin could serve as a Ca(2+)-activated signaling molecule that increases cellular excitability, which would in turn increase Ca2+ influx through the membrane. This is also the first known instance of a GTP-binding protein that binds Ca2+.
authors.affiliation: Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Nelson
authors.forename: S
authors.initials: S
authors.lastname: Cavallaro
authors.forename: C L
authors.initials: CL
authors.lastname: Yi
authors.forename: D
authors.initials: D
authors.lastname: McPhie
authors.forename: B G
authors.initials: BG
authors.lastname: Schreurs
authors.forename: P A
authors.initials: PA
authors.lastname: Gusev
authors.forename: A
authors.initials: A
authors.lastname: Favit
authors.forename: O
authors.initials: O
authors.lastname: Zohar
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Beushausen
authors.forename: G
authors.initials: G
authors.lastname: Ascoli
authors.forename: J
authors.initials: J
authors.lastname: Olds
authors.forename: R
authors.initials: R
authors.lastname: Neve
authors.forename: D L
authors.initials: DL
authors.lastname: Alkon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D015153:Blotting, Western; D029742:Caenorhabditis elegans Proteins; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016384:Consensus Sequence; D018076:DNA, Complementary; D049832:Decapodiformes; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009899:Optic Lobe, Nonmammalian / Q000166:cytology / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D012879:Skin Physiological Phenomena
chemical_list: D000906:Antibodies; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D006160:Guanosine Triphosphate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; C102751:cex-2 protein, C elegans; D002118:Calcium