Oligomerization of Ca-v beta subunits is an essential correlate of Ca2+ channel activity

Article

关键词: GATED CALCIUM-CHANNELS;    ALKALINE-PHOSPHATASE;    HEART;    MODULATION;    EXPRESSION;    COMPLEX;    HETEROGENEITY;    MECHANISM;    MODULE;   

DOI  :  10.1096/fj.10-165381

来源: SCIE

【 摘 要 】

Voltage-gated calcium channels conduct Ca2+ ions in response to membrane depolarization. The resulting transient increase in cytoplasmic free calcium concentration is a critical trigger for the initiation of such vital responses as muscle contraction and transcription. L-type Ca(v)1.2 calcium channels are complexes of the pore-forming alpha(1C) subunit associated with cytosolic Ca-v beta subunits. All major Ca-v beta s share a highly homologous membrane associated guanylate kinaselike (MAGUK) domain that binds to alpha(1C) at the alpha-interaction domain (AID), a short motif in the linker between transmembrane repeats I and II. In this study we show that Ca-v beta subunits form multimolecular homoand heterooligomeric complexes in human vascular smooth muscle cells expressing native calcium channels and in Cos7 cells expressing recombinant Ca(v)1.2 channel subunits. Ca-v beta s oligomerize at the alpha(1C) subunits residing in the plasma membrane and bind to the AID. However, Ca-v beta oligomerization occurs independently on the association with alpha(1C). Molecular structures responsible for Ca-v beta oligomerization reside in 3 regions of the guanylate kinase subdomain of MAGUK. An augmentation of Ca-v beta homooligomerization significantly increases the calcium current density, while heterooligomerization may also change the voltagedependence and inactivation kinetics of the channel. Thus, oligomerization of Ca-v beta subunits represents a novel and essential aspect of calcium channel regulation.-Lao, Q. Z., Kobrinsky, E., Liu, Z., Soldatov, N. M. Oligomerization of Ca-v beta subunits is an essential correlate of Ca2+ channel activity. FASEB J. 24, 5013-5023 (2010). www. fasebj. org

【 授权许可】

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