Journal article
γ1 Subunit Interactions within the Skeletal Muscle L-type Voltage-gated Calcium Channels
The Journal of biological chemistry, Vol.278(2), pp.1212-1219
01/10/2003
DOI: 10.1074/jbc.M208689200
PMID: 12409298
Abstract
Voltage-gated calcium channels mediate excitationcontraction coupling in the skeletal muscle. Their molecular composition, similar to neuronal channels, includes the pore-forming α1 and auxiliary α2δ, β, and γ subunits. The γ subunits are the least characterized, and their subunit interactions are unclear. The physiological importance of the neuronal γ is emphasized by epileptic stargazer mice that lack γ2. In this study, we examined the molecular basis of interaction between skeletal γ1 and the calcium channel. Our data show that the α11.1, β1a, and α2δ subunits are still associated in γ1 null mice. Reexpression of γ1 and γ2 showed that γ1, but not γ2, incorporates into γ1 null channels. By using chimeric constructs, we demonstrate that the first half of the γ1 subunit, including the first two transmembrane domains, is important for subunit interaction. Interestingly, this chimera also restores calcium conductance in γ1 null myotubes, indicating that the domain mediates both subunit interaction and current modulation. To determine the subunit of the channel that interacts with γ1, we examined the channel in muscular dysgenesis mice. Cosedimentation experiments showed that γ1 and α2δ are not associated. Moreover, α11.1 and γ1 subunits form a complex in transiently transfected cells, indicating direct interaction between the γ1 and α11.1 subunits. Our data demonstrate that the first half of γ1 subunit is required for association with the channel through α11.1. Because subunit interactions are conserved, these studies have broad implications for γ heterogeneity, function and subunit association with voltage-gated calcium channels.
Details
- Title: Subtitle
- γ1 Subunit Interactions within the Skeletal Muscle L-type Voltage-gated Calcium Channels
- Creators
- Jyothi Arikkath - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa, Iowa City, Iowa 52242Chien-Chang Chen - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa, Iowa City, Iowa 52242Christopher Ahern - Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706Valérie Allamand - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa, Iowa City, Iowa 52242Jason D Flanagan - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa, Iowa City, Iowa 52242Roberto Coronado - Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706Ronald G Gregg - Departments of Biochemistry and Molecular Biology and Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, Kentucky 40202Kevin P Campbell - Howard Hughes Medical Institute, Departments of Physiology and Biophysics and Neurology, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.278(2), pp.1212-1219
- DOI
- 10.1074/jbc.M208689200
- PMID
- 12409298
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 01/10/2003
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068276702771
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