Cited by 200Ion channel regulation and functionNeuroscience and Neuropharmacology ResearchCardiac electrophysiology and arrhythmias

Differential modulation of Cav2.1 channels by calmodulin and Ca2+-binding protein 1

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Lee, Amy, Westenbroek, Ruth E., Haeseleer, Françoise, Palczewski, Krzysztof, Scheuer, Todd, Catterall, William A.·2002·Nature Neuroscience

Abstract

Ca(v)2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM)-dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the neuronal Ca2+-binding protein 1 (CaBP1) modulates Ca(v)2.1 channels in a manner that is markedly different from modulation by CaM. CaBP1 enhances inactivation, causes a depolarizing shift in the voltage dependence of activation, and does not support Ca2+-dependent facilitation of Ca(v)2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the alpha1 subunit of Ca(v)2.1 channels (alpha12.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha12.1 from transfected cells and brain extracts, and colocalizes with alpha12.1 in discrete microdomains of neurons in the hippocampus and cerebellum. Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons.

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Crossref · 10.1038/nn805

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  • CaBP1 increases inactivation of P/Q-type Ca2+ channels, whereas VILIP-2 slows the rate of Ca2+ channel inactivation and enhances facilitation.

    “In addition, another EF-hand Ca2+-binding protein called “calcium-binding protein 1” (CaBP1) increases inactivation of P/Q-type Ca2+ channels (Lee et al., 2002), whereas a third EF-hand Ca2+-binding protein called visinin-like protein 2 (VILIP-2) slows the rate of Ca2+ channel inactivation and enhances facilitation (Lautermilch et al., 2005).”

    From The Presynaptic Active Zone (2012) · cites this paper as Lee et al., 2002

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Authors
Lee, A., Westenbroek, R. E., Haeseleer, F., Palczewski, K., Scheuer, T., & Catterall, W. A.
Affiliations
University of Washington (US)
Corresponding author
Catterall, William A.
Venue
Nature Neuroscience
Published
2002-02-04
Volume
5
Issue
3
Pages
210-217
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2096264533
Cited by
200
References
41
Citations by year
2025: 3 · 2024: 18 · 2023: 6 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 12 · 2013: 8 · 2012: 9
FWCI
4.17
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Eye Institute (R01EY008061, R01 EY08061)
  • National Institute of Neurological Disorders and Stroke (F32NS010645, F32 NS10645, R0-1 NS22625, R01NS022625)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
P/Q-type calcium channels, calmodulin, CaM-binding domain, alpha1 subunit, voltage dependence of activation, synaptic plasticity, calcium influx, hippocampus, cerebellum, protein-protein interaction
MeSH terms
Animals, Brain, Calcium, Calcium-Binding Proteins, Calmodulin, Cell Line, Cerebellum, Chelating Agents, Egtazic Acid, Hippocampus, Humans, Male, Models, Molecular, Neurons, Protein Binding, Protozoan Proteins, Rats, Sprague-Dawley, Protein Structure, Secondary, Patch-Clamp Techniques, Two-Hybrid System Techniques, Calcium Channels, N-Type, Protein Subunits, Rats

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