Journal article
Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel α12.1 subunit
FEBS letters, Vol.532(3), pp.300-308
12/18/2002
DOI: 10.1016/S0014-5793(02)03693-1
PMID: 12482583
Abstract
We characterized the neuronal two-domain (95kD-α12.1) form of the α12.1 subunit of the voltage-gated calcium channels using genetic and molecular analysis. The 95kD-α12.1 is absent in neuronal preparations from CACNA1A null mouse demonstrating that α12.1 and 95kD-α12.1 arise from the same gene. A recombinant two-domain form (α1AI-II) of α12.1 associates with the β subunit and is trafficked to the plasma membrane. Translocation of the α1AI-II to the plasma membrane requires association with the β subunit, since a mutation in the α1AI-II that inhibits β subunit association reduces membrane trafficking. Though the α1AI-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) 6935–6940]. In this study, we demonstrate that co-expression of the α1AI-II significantly reduces the current amplitude of α12.1/β1a/α2δ channels, via competition for the β subunit. Taken together, our results demonstrate a dual functional role for the α1AI-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-α12.1 in altering synaptic activity via protein–protein interactions and/or regulation of P/Q-type currents.
Details
- Title: Subtitle
- Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel α12.1 subunit
- Creators
- Jyothi Arikkath - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa College of Medicine, 400 Eckstein Medical Research Building, Iowa City, IA 52242-1101, USARicardo Felix - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa College of Medicine, 400 Eckstein Medical Research Building, Iowa City, IA 52242-1101, USAChristopher Ahern - Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USAChien-Chang Chen - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa College of Medicine, 400 Eckstein Medical Research Building, Iowa City, IA 52242-1101, USAYasuo Mori - Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, JapanInseon Song - National CRI Center for Calcium and Learning, Korea Institute of Science and Technology, Seoul, South KoreaHee-Sup Shin - National CRI Center for Calcium and Learning, Korea Institute of Science and Technology, Seoul, South KoreaRoberto Coronado - Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USAKevin P Campbell - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa College of Medicine, 400 Eckstein Medical Research Building, Iowa City, IA 52242-1101, USA
- Resource Type
- Journal article
- Publication Details
- FEBS letters, Vol.532(3), pp.300-308
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S0014-5793(02)03693-1
- PMID
- 12482583
- ISSN
- 0014-5793
- eISSN
- 1873-3468
- Language
- English
- Date published
- 12/18/2002
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068269502771
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