Cavβ1
Description: calcium channel, voltage-dependent, beta 1 subunit Gene: cacnb1 Alias: cacnb1, CAB1, CACNLB1, CCHLB1
CACNB1 (also known as CAB1; CCHLB1; CACNLB1; MGC41896) encodes a calcium channel beta subunit. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified.
http://www.ncbi.nlm.nih.gov/gene/782
Gene
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_000723.5 | 3711 | |
| Mouse | NM_031173.4 | 1873 | |
| Rat | NM_017346.1 | 3293 |
Protein Isoforms
Isoforms
Post-Translational Modifications
CaV1.1 is a large transmembrane protein which contains both the Ca2+ conducting pore and the voltage sensing S4 domain. Four other auxiliary subunits bind CaV1.1 to make up DHPR (dihydropyridine receptor, that serves as a modest L-type Ca2+ channel but is primarily known for its function as a voltage sensor. For review, see Flucher et al. 2005 [1253]), with the most widely studied being the cytosolic CaVβ1a (cacnb1) subunit. CaVβ1a, a muscle specific member of the CaVβ family of proteins, binds to a region of the I–II intracellular loop of CaV1.1 known as the alpha interaction domain (AID) (Chen et al. 2004 [1254]). The correct organization of CaV1.1 into tetrads within the t-tubule membrane is a specific function of the CaVβ1a isoform (Schredelseker et al. 2005 [1255]).
Cavβ1 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
The b1a subunit is one of the auxiliary subunits of CaV1.1 channels (Isom et al. 1994 [1247] and see Channelpedia entry of Cav1.1) and the main isoform among the b1 subunits present in muscle (Ren & Hall, 1997 [1248]).
CaVβ1a expression is highly increased in old mice (Taylor [1249]).
The b1a subunit has important effects on the surface expression of alpha-1 subunits, e.g. Cav1.1. cacnb1 subunit produces major changes in the amplitude of L-type currents without any effect on charge movement. (García [234])
Although classically known for augmenting the expression and function of CaV1 subfamily of calcium channels, the CaVβ family of subunits may contribute to the down-regulation of CaV1 as well (Taylor et al. [1249]). A family of Ras-related G-proteins (RGKs) mediate the down-regulation of several CaV1 isoforms in a CaVβ dependent manner (Beguin et al. 2001 [504]). Additionally, the previously uncharacterized SH3 domain of CaVβ was shown to bind dynamin and mediate endocytosis of CaV1.2 (Gonzalez-Gutierrez et al. 2007 [1256]).
CaVβ1a is classically described by its role in chaperoning CaV1.1 to the plasma membrane and regulating L-type Ca2+ current (Gregg et al. 1996 [1257]; Strube et al. 1996 [1258]; Beurg et al. 1997 [1259]; Neuhuber et al. 1998 [1260]). Most notably, excitation-contraction (E-C) coupling cannot occur without CaVβ1a (Gregg et al. 1996 [1257]). CaVβ1a binds to charged residues on RyR (Cheng et al. 2005 [1254]) and neutralization of these residues reduces E-C coupling, suggesting a direct interaction with ryanodine receptor (RyR). The correct organization of CaV1.1 into tetrads within the t-tubule membrane is also a specific function of the CaVβ1a isoform (Schredelseker et al. 2005 [1255]).
Experimental overexpression of CaVβ1a reduces both the expression of CaV1.1 and specific force in dissociated single fibers of young mice. Additionally, siRNA inhibition of CaVβ1a restores charge movement in aged muscle. These findings suggest that overexpression of CaVβ1a with aging contributes to excitation-contraction uncoupling by reducing the level of CaV1.1. (Taylor [1249])
References
The beta1a subunit regulates the functional properties of adult frog and mouse L-type Ca2+ channels of skeletal muscle.
J. Physiol. (Lond.), 2002 Dec 1 , 545 (407-19).
Béguin P
et al.
Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem.
Nature,
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7
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Strube C
Absence of regulation of the T-type calcium current by Cav1.1, beta1a and gamma1 dihydropyridine receptor subunits in skeletal muscle cells.
Pflugers Arch.,
2008
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, 455 (921-7).
Isom LL
et al.
Auxiliary subunits of voltage-gated ion channels.
Neuron,
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, 12 (1183-94).
Ren D
et al.
Functional expression and characterization of skeletal muscle dihydropyridine receptors in Xenopus oocytes.
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1997
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5
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Taylor JR
et al.
Increased CaVbeta1A expression with aging contributes to skeletal muscle weakness.
Aging Cell,
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, 8 (584-94).
Xie D
et al.
Subunits of voltage-gated calcium channels in murine spiral ganglion cells.
Acta Otolaryngol.,
2007
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, 127 (8-12).
Zhou W
et al.
Non-sense mutations in the dihydropyridine receptor beta1 gene, CACNB1, paralyze zebrafish relaxed mutants.
Cell Calcium,
2006
Mar
, 39 (227-36).
García MC
et al.
Short-term regulation of excitation-contraction coupling by the beta1a subunit in adult mouse skeletal muscle.
Biophys. J.,
2005
Dec
, 89 (3976-84).
Flucher BE
et al.
The role of auxiliary dihydropyridine receptor subunits in muscle.
J. Muscle Res. Cell. Motil.,
2005
, 26 (1-6).
Chen YH
et al.
Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels.
Nature,
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10
, 429 (675-80).
Schredelseker J
et al.
The beta 1a subunit is essential for the assembly of dihydropyridine-receptor arrays in skeletal muscle.
Proc. Natl. Acad. Sci. U.S.A.,
2005
Nov
22
, 102 (17219-24).
González-Gutiérrez G
et al.
The Src homology 3 domain of the beta-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction.
J. Biol. Chem.,
2007
Jan
26
, 282 (2156-62).
Gregg RG
et al.
Absence of the beta subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the alpha 1 subunit and eliminates excitation-contraction coupling.
Proc. Natl. Acad. Sci. U.S.A.,
1996
Nov
26
, 93 (13961-6).
Strube C
et al.
Reduced Ca2+ current, charge movement, and absence of Ca2+ transients in skeletal muscle deficient in dihydropyridine receptor beta 1 subunit.
Biophys. J.,
1996
Nov
, 71 (2531-43).
Beurg M
et al.
Recovery of Ca2+ current, charge movements, and Ca2+ transients in myotubes deficient in dihydropyridine receptor beta 1 subunit transfected with beta 1 cDNA.
Biophys. J.,
1997
Aug
, 73 (807-18).
Neuhuber B
et al.
Association of calcium channel alpha1S and beta1a subunits is required for the targeting of beta1a but not of alpha1S into skeletal muscle triads.
Proc. Natl. Acad. Sci. U.S.A.,
1998
Apr
28
, 95 (5015-20).
Credits
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