Arikkath, J Felix, R Ahern, C Chen, CC Mori, Y Song, I Shin, HS Coronado, R Campbell, KP 2024-01-21T09:36:43Z 2024-01-21T09:36:43Z 2021-09-01 2002-12-18 0014-5793 https://pubs.kist.re.kr/handle/201004/138962 We characterized the neuronal two-domain (95kD-alpha(1)2.1) form of the alpha(1)2.1 subunit of the voltage-gated calcium channels using genetic and molecular analysis. The 95kD-alpha(1)2.1 is absent in neuronal preparations from CACNA1A null mouse demonstrating that alpha(1)2.1 and 95kD-alpha(1)2.1 arise from the same gene. A recombinant two-domain form (alpha(1AI-II)) of alpha(1)2.1 associates with the beta subunit and is trafficked to the plasma membrane. Translocation of the alpha(1AI-II) to the plasma membrane requires association with the beta subunit, since a mutation in the alpha(1AI-II) that inhibits beta subunit association reduces membrane trafficking. Though the alpha(1AI-II) protein does not conduct any voltage-gated currents, we have previously shown that it generates a high density of non-linear charge movements [Ahern et al., Proc. Natl. Acad. Sci. USA 98 (2001) 6935-69401. In this study, we demonstrate that co-expression of the alpha(1AI-II) Significantly reduces the current amplitude of (alpha(1) 2.1/beta(1a)/alpha(2)delta channels, via competition for the beta subunit. Taken together, our results demonstrate a dual functional role for the alpha(1AI-II) protein, both as a voltage sensor and modulator of P/Q-type currents in recombinant systems. These studies suggest an in vivo role for the 95kD-alpha(1)2.1 in altering synaptic activity via protein-protein interactions and/or regulation of P/Q-type currents. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. English ELSEVIER SCIENCE BV CA2+ CHANNELS BETA-SUBUNIT SKELETAL-MUSCLE GAMMA-SUBUNIT N-TYPE SYNAPTIC TRANSMISSION MICE LACKING IDENTIFICATION PROTEIN BRAIN Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel alpha(1)2.1 subunit Article 10.1016/S0014-5793(02)03693-1 1 FEBS LETTERS, v.532, no.3, pp.300 - 308 FEBS LETTERS 532 3 300 308 scie scopus 000179884800008 2-s2.0-0037132497 Biochemistry & Molecular Biology Biophysics Cell Biology Biochemistry & Molecular Biology Biophysics Cell Biology Article CA2+ CHANNELS BETA-SUBUNIT SKELETAL-MUSCLE GAMMA-SUBUNIT N-TYPE SYNAPTIC TRANSMISSION MICE LACKING IDENTIFICATION PROTEIN BRAIN 95kD-alpha(1)2.1 two-domain subunit episodic ataxia type 2 calcium channels