Calmodulin-dependent gating of Ca^sub v^1.2 calcium channels in the absence of Ca^sub v^[beta] subunits
It is generally accepted that to generate calcium currents in response to depolarization, Ca...1.2 calcium channels require association of the pore-forming 1C subunit with accessory Ca...β and 2 subunits. A single calmodulin (CaM) molecule is tethered to the C-terminal α...-LA/IQ region and mediates...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-06, Vol.105 (23), p.8154 |
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Sprache: | eng |
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Zusammenfassung: | It is generally accepted that to generate calcium currents in response to depolarization, Ca...1.2 calcium channels require association of the pore-forming 1C subunit with accessory Ca...β and 2 subunits. A single calmodulin (CaM) molecule is tethered to the C-terminal α...-LA/IQ region and mediates ...-dependent inactivation of the channel. Ca...β subunits are stably associated with the α...-interaction domain site of the cytoplasmic linker between internal repeats I and II and also interact dynamically, in a ...-dependent manner, with the α...-IQ region. Here, we describe a surprising discovery that coexpression of exogenous CaM (CaM...) with α.../α... in COS1 cells in the absence of Ca...β subunits stimulates the plasma membrane targeting of α..., facilitates calcium channel gating, and supports ...-dependent inactivation. Neither real-time PCR with primers complementary to monkey Ca...β subunits nor coimmunoprecipitation analysis with exogenous α... revealed an induction of endogenous Ca...β subunits that could be linked to the effect of CaM... Coexpression of a calcium-insensitive CaM mutant CaM... also facilitated gating of Ca...β-free Ca...1.2 channels but did not support ...-dependent inactivation. Our results show there is a functional matchup between CaM... and Ca...β subunits that, in the absence of Ca...β, renders ... channel gating facilitated by CaM molecules other than the one tethered to LA/IQ to support ...-dependent inactivation. Thus, coexpression of CaM... creates conditions when the channel gating, voltage- and ...-dependent inactivation, and plasma-membrane targeting occur in the absence of Ca...β. We suggest that CaM... affects specific Ca...β-free conformations of the channel that are not available to endogenous CaM. (ProQuest: ... denotes formulae/symbols omitted.) |
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ISSN: | 0027-8424 1091-6490 |