Genomes and Genes
Gene Symbol: Cacna1b
Description: calcium voltage-gated channel subunit alpha1 B
Alias: BIII, voltage-dependent N-type calcium channel subunit alpha-1B, brain calcium channel III, calcium channel, L type, alpha-1 polypeptide, calcium channel, voltage-dependent, N type, alpha 1B subunit, voltage gated N-type calcium channel Ca(v)2.2, voltage-gated calcium channel subunit alpha Cav2.2
- Lewis R, Nielsen K, Craik D, Loughnan M, Adams D, Sharpe I, et al. Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem. 2000;275:35335-44 pubmed..1)H NMR studies reveal that CVID possesses a combination of unique structural features, including two hydrogen bonds that stabilize loop 2 and place loop 2 proximal to loop 4, creating a globular surface that is rigid and well defined. ..
- Scheuber A, Miles R, Poncer J. Presynaptic Cav2.1 and Cav2.2 differentially influence release dynamics at hippocampal excitatory synapses. J Neurosci. 2004;24:10402-9 pubmed..2 by G(o/i), thereby increasing the number of available channels. ..
- Ishii M, Hagiwara T, Mori Y, Shimizu S. Involvement of TRPM2 and L-type Ca²? channels in Ca²? entry and cell death induced by hydrogen peroxide in rat ?-cell line RIN-5F. J Toxicol Sci. 2014;39:199-209 pubmed..Our results suggest that TRPM2 channels rather than L-type Ca²? channels primarily contribute to H?O?-induced Ca²? entry and cell death. ..
- Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer R, Gottmann K, et al. Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature. 2003;423:939-48 pubmed..These data suggest that alpha-neurexins organize presynaptic terminals by functionally coupling Ca2+ channels to the presynaptic machinery. ..
- Raingo J, Castiglioni A, Lipscombe D. Alternative splicing controls G protein-dependent inhibition of N-type calcium channels in nociceptors. Nat Neurosci. 2007;10:285-92 pubmed..Here we show that preferential inclusion in nociceptors of exon 37a in rat Cacna1b (encoding Ca(V)2.2) creates, de novo, a C-terminal module that mediates voltage-independent inhibition...
- Rebolledo Antúnez S, Farías J, Arenas I, Garcia D. Gating charges per channel of Ca(V)2.2 channels are modified by G protein activation in rat sympathetic neurons. Arch Biochem Biophys. 2009;486:51-7 pubmed publisher..This paper shows for the first time a significant and reversible decrease in charge transfer of Ca(V)2.2 channels under G protein modulation, which might depend on the activated G protein inhibitory pathway. ..
- Ino M, Yoshinaga T, Wakamori M, Miyamoto N, Takahashi E, Sonoda J, et al. Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels. Proc Natl Acad Sci U S A. 2001;98:5323-8 pubmed
- Cassidy J, Ferron L, Kadurin I, Pratt W, Dolphin A. Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary Î±2Î´-1 subunits. Proc Natl Acad Sci U S A. 2014;111:8979-84 pubmed publisher..2 and Î±2Î´-1 is not disrupted by gabapentin. Altogether, these results demonstrate that CaV2.2 and Î±2Î´-1 are intimately associated at the plasma membrane and allow us to infer a region of interaction. ..
- Khanna R, Li Q, Bewersdorf J, Stanley E. The presynaptic CaV2.2 channel-transmitter release site core complex. Eur J Neurosci. 2007;26:547-59 pubmed..2 in situ are also the most intimately attached. Our findings suggest that the CaV2.2 cluster is an integral element of a multimolecular vesicle-fusion module that forms the core of a multifunctional TRS. ..
- Snutch T, Leonard J, Gilbert M, Lester H, Davidson N. Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sci U S A. 1990;87:3391-5 pubmed..The antisense oligonucleotide experiments specifically show that one or several of the Ca-channel classes are related to the Ca channels observed in rat brain mRNA injected oocytes. ..
- Page K, Rothwell S, Dolphin A. The CaV? Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination. J Biol Chem. 2016;291:20402-16 pubmed publisher..We propose that targeting to the plasma membrane requires a conformational change in the I-II loop that is induced by binding of the CaV? subunit. ..
- Hell J, Appleyard S, Yokoyama C, Warner C, Catterall W. Differential phosphorylation of two size forms of the N-type calcium channel alpha 1 subunit which have different COOH termini. J Biol Chem. 1994;269:7390-6 pubmed..Specific phosphorylation of the long form of the class B alpha 1 subunit by CaM kinase II may differentially regulate the function of N-type calcium channels containing different size forms of their alpha 1 subunits in vivo. ..
- Waithe D, Ferron L, Page K, Chaggar K, Dolphin A. Beta-subunits promote the expression of Ca(V)2.2 channels by reducing their proteasomal degradation. J Biol Chem. 2011;286:9598-611 pubmed publisher..In conclusion, there is a marked effect of ?-subunits on Ca(V)2.2 expression, particularly in neurites, but our results point to protection from proteasomal degradation rather than masking of an ER retention signal. ..
- Lin Z, Lin Y, Schorge S, Pan J, Beierlein M, Lipscombe D. Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons. J Neurosci. 1999;19:5322-31 pubmed
- Saegusa H, Matsuda Y, Tanabe T. Effects of ablation of N- and R-type Ca(2+) channels on pain transmission. Neurosci Res. 2002;43:1-7 pubmed..3-/- mice, was also observed in the Ca(v)2.2-/- mice. Therefore, it is suggested that these mutant mice could provide novel models to delineate the nociceptive and antinociceptive mechanisms. ..
- Su X, Leon L, Laping N. Role of spinal Cav2.2 and Cav2.1 ion channels in bladder nociception. J Urol. 2008;179:2464-9 pubmed publisher..However, agatoxin and verapamil were less effective. The study suggests that spinal Cav2.2 and Q-type Cav2.1 calcium channels contribute to acute bladder nociception, while Cav1 channels have a limited role. ..
- Bucci G, Mochida S, Stephens G. Inhibition of synaptic transmission and G protein modulation by synthetic CaV2.2 Ca²+ channel peptides. J Physiol. 2011;589:3085-101 pubmed publisher..2 amino terminal and I-II loop contribute molecular determinants for Ca2+ channel function; the data favour a direct interaction of peptides with Ca2+ channels to inhibit synaptic transmission and attenuate G protein modulation. ..
- Beuckmann C, Sinton C, Miyamoto N, Ino M, Yanagisawa M. N-type calcium channel alpha1B subunit (Cav2.2) knock-out mice display hyperactivity and vigilance state differences. J Neurosci. 2003;23:6793-7 pubmed..2-/- mice. These results indicate a role of the N-type Ca2+ channel in activity and vigilance state control, which we interpret in terms of effects on neurotransmitter release. ..
- Vivas O, Castro H, Arenas I, Elías Viñas D, Garcia D. PIP? hydrolysis is responsible for voltage independent inhibition of CaV2.2 channels in sympathetic neurons. Biochem Biophys Res Commun. 2013;432:275-80 pubmed publisher..These results support that the hydrolysis of PIP(2) is responsible for the voltage independent inhibition of Ca(V)2.2 channels. ..
- Hernández Castellanos J, Vivas O, Garduño J, De la Cruz L, Arenas I, Elías Viñas D, et al. G?? mimics activation kinetic slowing of CaV2.2 channels by noradrenaline in rat sympathetic neurons. Biochem Biophys Res Commun. 2014;445:250-4 pubmed publisher..These results advance our understanding on the mechanisms by which signals conveying from a variety of membrane receptors are able to display precise homeostatic responses. ..
- Lai M, Wang F, Rohan J, Maeno Hikichi Y, Chen Y, Zhou Y, et al. A tctex1-Ca2+ channel complex for selective surface expression of Ca2+ channels in neurons. Nat Neurosci. 2005;8:435-42 pubmed..These results underscore the importance of the specific tctex1-channel interaction in determining sorting and trafficking of neuronal Ca(2+) channels with different functionalities. ..
- Burgess D, Biddlecome G, McDonough S, Diaz M, Zilinski C, Bean B, et al. beta subunit reshuffling modifies N- and P/Q-type Ca2+ channel subunit compositions in lethargic mouse brain. Mol Cell Neurosci. 1999;13:293-311 pubmed..The existence of beta subunit reshuffling demonstrates that molecular plasticity of Ca2+ channel assembly, a normal feature of early brain development, is retained in the mature brain. ..
- N GOUEMO P, Morad M. Voltage-gated calcium channels in adult rat inferior colliculus neurons. Neuroscience. 2003;120:815-26 pubmed..We conclude that IC neurons express functionally all members of HVA Ca(2+) channels, but only a subset of these neurons appear to have developed functional LVA channels. ..
- Maingret F, Coste B, Hao J, Giamarchi A, Allen D, Crest M, et al. Neurotransmitter modulation of small-conductance Ca2+-activated K+ channels by regulation of Ca2+ gating. Neuron. 2008;59:439-49 pubmed publisher..Hence, neurotransmitter-initiated signaling cascades can dynamically regulate Ca2+ sensitivity of SK channels and directly influence somatic excitability. ..
- Bell T, Thaler C, Castiglioni A, Helton T, Lipscombe D. Cell-specific alternative splicing increases calcium channel current density in the pain pathway. Neuron. 2004;41:127-38 pubmed..8. Cell-specific inclusion of exon 37a correlates closely with significantly larger N-type currents in nociceptive neurons. This unique splice isoform of the N-type channel could represent a novel target for pain management. ..
- Gandini M, Henríquez D, Grimaldo L, Sandoval A, Altier C, Zamponi G, et al. CaV2.2 channel cell surface expression is regulated by the light chain 1 (LC1) of the microtubule-associated protein B (MAP1B) via UBE2L3-mediated ubiquitination and degradation. Pflugers Arch. 2014;466:2113-26 pubmed publisher..Together these results revealed a novel functional coupling between LC1 and the N-type channels. ..
- Pan J, Lipscombe D. Alternative splicing in the cytoplasmic II-III loop of the N-type Ca channel alpha 1B subunit: functional differences are beta subunit-specific. J Neurosci. 2000;20:4769-75 pubmed..The potential to mix and match multiple alpha(1B) splice variants and beta subunits probably represents a mechanism for controlling the plasticity of excitation-secretion coupling at different synapses. ..
- Latour I, Hamid J, Beedle A, Zamponi G, MacVicar B. Expression of voltage-gated Ca2+ channel subtypes in cultured astrocytes. Glia. 2003;41:347-53 pubmed..Overall, our data indicate that astrocytes express multiple types of voltage-gated Ca(2+) channels, hinting at a complex regulation of Ca(2+) homeostasis in glial cells. ..
- Coppola T, Magnin Luthi S, Perret Menoud V, Gattesco S, Schiavo G, Regazzi R. Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. J Biol Chem. 2001;276:32756-62 pubmed..We propose that the Rab3 effector RIM is a scaffold protein that participates through its multiple binding partners in the docking and fusion of secretory vesicles at the release sites. ..
- Asadi S, Javan M, Ahmadiani A, Sanati M. Alternative splicing in the synaptic protein interaction site of rat Ca(v)2.2 (alpha (1B)) calcium channels: changes induced by chronic inflammatory pain. J Mol Neurosci. 2009;39:40-8 pubmed publisher..Determining different Ca(v)2.2 splice variants in rat nervous system and the impact of inflammatory pain on the splicing pattern suggest a possible regulatory role for calcium channel alternative splicing. ..
- Lin Z, Haus S, Edgerton J, Lipscombe D. Identification of functionally distinct isoforms of the N-type Ca2+ channel in rat sympathetic ganglia and brain. Neuron. 1997;18:153-66 pubmed
- Li D, Wang F, Lai M, Chen Y, Zhang J. A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C. J Neurosci. 2005;25:1914-23 pubmed..Thus, the PP2calpha-Ca2+ channel complex is responsible for rapid dephosphorylation of Ca2+ channels and may contribute to regulation of synaptic transmission in neurons. ..
- Goo Y, Lim W, Elmslie K. Ca2+ enhances U-type inactivation of N-type (CaV2.2) calcium current in rat sympathetic neurons. J Neurophysiol. 2006;96:1075-83 pubmed..Taken together, the data support a role for extracellular divalent cations in modulating U-type inactivation. CDI appears to play a role in N-channel inactivation, but on a slower (sec) time scale. ..
- Murakami M, Nakagawasai O, Suzuki T, Mobarakeh I, Sakurada Y, Murata A, et al. Antinociceptive effect of different types of calcium channel inhibitors and the distribution of various calcium channel alpha 1 subunits in the dorsal horn of spinal cord in mice. Brain Res. 2004;1024:122-9 pubmed..The results of this study revealed the localization and functions of several calcium channels that are involved in nociceptive neurotransmission within the dorsal horn of the mouse spinal cord. ..
- Samuels B, Hsueh Y, Shu T, Liang H, Tseng H, Hong C, et al. Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron. 2007;56:823-37 pubmed..Functional consequences include alterations in calcium influx. Mechanistically, Cdk5 regulates the interaction between CASK and liprin-alpha. These results provide a molecular explanation of how Cdk5 can promote synaptogenesis. ..
- Khanna R, Zougman A, Stanley E. A proteomic screen for presynaptic terminal N-type calcium channel (CaV2.2) binding partners. J Biochem Mol Biol. 2007;40:302-14 pubmed..Our results suggest that the channel is anchored to a cytoplasmic matrix related to the previously described particle web. ..
- Song L, Espinoza Fuenzalida I, Etheridge S, Jones O, Fitzgerald E. The R-Domain: Identification of an N-terminal Region of the Î±2Î´-1 Subunit Which is Necessary and Sufficient for its Effects on Cav2.2 Calcium Currents. Curr Mol Pharmacol. 2015;8:169-79 pubmed..We suggest, therefore, that Rd likely constitutes the major locus for physical interaction with the Î±1 subunit and may provide a target for novel Cav therapeutics. ..
- Davies J, Jarvis S, Zamponi G. Bipartite syntaxin 1A interactions mediate CaV2.2 calcium channel regulation. Biochem Biophys Res Commun. 2011;411:562-8 pubmed publisher..Furthermore, we highlight the syntaxin 1A N-terminus as the minimal determinant for functional regulation of Ca(V)2.2 and Ca(V)2.3 channels. ..
- Rehn M, Bader S, Bell A, Diener M. Distribution of voltage-dependent and intracellular Ca2+ channels in submucosal neurons from rat distal colon. Cell Tissue Res. 2013;353:355-66 pubmed publisher..Thus, rat submucosal neurons are equipped with various types of high-voltage activated Ca(v) channels and with IP3 receptors for intracellular Ca2+ signaling. ..
- Nudler S, Pagani M, Urbano F, McEnery M, Uchitel O. Testosterone modulates Ca(v2.2) calcium channels' functional expression at rat levator ani neuromuscular junction. Neuroscience. 2005;134:817-26 pubmed..2) and transmitter release at the neuromuscular junctions of these sexually dimorphic motoneurons. ..
- Martin Moutot N, Haro L, Santos R, Mori Y, Seagar M. Phoneutria nigriventer omega-Phonetoxin IIA: a new tool for anti-calcium channel autoantibody assays in Lambert-Eaton myasthenic syndrome. Neurobiol Dis. 2006;22:57-63 pubmed..1 and/or Cav2.2 antibodies detected using two different omega-conotoxins. Thus, the 125I-omegaPtxIIA assay detects a broader spectrum of autoantibody specificities than current omega-conotoxin-based assays...
- Ohno S, Yokoi H, Mori K, Kasahara M, Kuwahara K, Fujikura J, et al. Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure. Sci Rep. 2016;6:27192 pubmed publisher..In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes. ..
- Zhou M, Bavencoffe A, Pan H. Molecular Basis of Regulating High Voltage-Activated Calcium Channels by S-Nitrosylation. J Biol Chem. 2015;290:30616-23 pubmed publisher..S-Nitrosylation mediates the feedback regulation of N-type channels by NO. ..
- Thomas J, Hagen J, Soh D, Lee A. Molecular moieties masking Ca2+-dependent facilitation of voltage-gated Cav2.2 Ca2+ channels. J Gen Physiol. 2018;150:83-94 pubmed publisher..Our results reveal a functional divergence in the CDF regulatory domains of Cav2 channels, which may help to diversify the modes by which Cav2.1 and Cav2.2 can modify synaptic transmission. ..
- Kornek B, Storch M, Bauer J, Djamshidian A, Weissert R, Wallstroem E, et al. Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis. Brain. 2001;124:1114-24 pubmed..Our data suggest that calcium influx through voltage-dependent calcium channels is one possible candidate mechanism for axonal degeneration in inflammatory demyelinating disorders. ..
- N GOUEMO P, Yasuda R, Morad M. Ethanol withdrawal is accompanied by downregulation of calcium channel alpha 1B subunit in rat inferior colliculus neurons. Brain Res. 2006;1108:216-20 pubmed..Thus, remodeling of N-type Ca(2+) channels may play an important role in neuronal hyperexcitability that leads to ethanol withdrawal seizures. ..
- Mallmann R, Wilmes T, Lichvárová L, Bührer A, Lohmüller B, Castonguay J, et al. Tetraspanin-13 modulates voltage-gated CaV2.2 Ca2+ channels. Sci Rep. 2013;3:1777 pubmed publisher..2. These data indicate that TSPAN-13 might regulate CaV2.2 Ca(2+) channel activity in defined synaptic membrane compartments and thereby influences transmitter release. ..
- Chapman E, Desai R, Davis A, Tornehl C. Delineation of the oligomerization, AP-2 binding, and synprint binding region of the C2B domain of synaptotagmin. J Biol Chem. 1998;273:32966-72 pubmed..These studies provide the first structural information regarding C2B target protein recognition and provide the means to selectively disrupt synaptotagmin-effector interactions for functional studies. ..
- Biederer T, Sudhof T. Mints as adaptors. Direct binding to neurexins and recruitment of munc18. J Biol Chem. 2000;275:39803-6 pubmed..Our data support a model whereby one of the functions of Mints is to localize the vesicle fusion protein Munc18 to those sites at the plasma membrane that are defined by neurexins, presumably in the vicinity of points of exocytosis. ..
- D Arco M, Margas W, Cassidy J, Dolphin A. The upregulation of Î±2Î´-1 subunit modulates activity-dependent Ca2+ signals in sensory neurons. J Neurosci. 2015;35:5891-903 pubmed publisher..2 channels. Thus, by controlling channel abundance at the plasma membrane, the Î±2Î´-1 subunit has a major impact on the organization of depolarization-induced intracellular Ca(2+) signaling in dorsal root ganglion neurons. ..
- Leenders A, Lin L, Huang L, Gerwin C, Lu P, Sheng Z. The role of MAP1A light chain 2 in synaptic surface retention of Cav2.2 channels in hippocampal neurons. J Neurosci. 2008;28:11333-46 pubmed publisher..2 to the actin cytoskeleton, thus contributing to presynaptic function. ..
- Witkovsky P, Shen C, McRory J. Differential distribution of voltage-gated calcium channels in dopaminergic neurons of the rat retina. J Comp Neurol. 2006;497:384-96 pubmed..Our findings are consistent with the available pharmacological data indicating that alpha1A and alpha1B calcium channels control the major fraction of dopamine release in the rat retina. ..
- Brittain J, Wang Y, Eruvwetere O, Khanna R. Cdk5-mediated phosphorylation of CRMP-2 enhances its interaction with CaV2.2. FEBS Lett. 2012;586:3813-8 pubmed publisher..Cdk5-phosphorylated CRMP-2 had increased association with CaV2.2. These results identify an important role for Cdk5 in CRMP2-mediated CaV2.2 regulation. ..
- Altier C, Dale C, Kisilevsky A, Chapman K, Castiglioni A, Matthews E, et al. Differential role of N-type calcium channel splice isoforms in pain. J Neurosci. 2007;27:6363-73 pubmed..In contrast, both N-type channel isoforms (e37a- and e37b-containing) contribute to tactile neuropathic allodynia. Hence, exon 37a acts as a molecular switch that tailors the channels toward specific roles in pain. ..
- Dubel S, Starr T, Hell J, Ahlijanian M, Enyeart J, Catterall W, et al. Molecular cloning of the alpha-1 subunit of an omega-conotoxin-sensitive calcium channel. Proc Natl Acad Sci U S A. 1992;89:5058-62 pubmed..This brain Ca channel may mediate the omega-conotoxin-sensitive Ca influx required for neurotransmitter release at many synapses. ..