The molecular chaperone hsp70 interacts with the cytosolic II-III loop of the Cav2.3 E-type voltagegated Ca2+ channel

被引:22
作者
Krieger, A
Radhakrishnan, K
Pereverzev, A
Siapich, SA
Banat, M
Kamp, MA
Leroy, J
Klöckner, U
Hescheler, J
Weiergräber, M
Schneider, T
机构
[1] Univ Cologne, Inst Neurophysiol, D-50931 Cologne, Germany
[2] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany
[3] Univ Cologne, Inst Vegetat Physiol, D-50931 Cologne, Germany
[4] Univ Western Ontario, Canadian Inst Hlth Res Grp Skeletal Dev & Remodel, Dept Physiol & Pharmacol, Fac Med & Dent, London, ON N6A 3K7, Canada
[5] CNRS, UMR 6542, Fac Sci, F-75700 Paris, France
[6] Univ Halle Wittenberg, Julius Bernstein Inst Physiol, Halle, Germany
关键词
protein interaction; 15-deoxyspergualin; toxin-resistant current; R-type; secretion; protein kinase C; facilitation;
D O I
10.1159/000092071
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Multiple types of voltage-activated Ca2+ channels (T, L, N, P, Q, R type) coexist in excitable cells and participate in synaptic differentiation, secretion, transmitter release, and neuronal plasticity. Ca2+ ions entering cells trigger these events through their interaction with the ion channel itself or through Ca2+ binding to target proteins initiating signalling cascades at cytosolic loops of the ion conducting subunit (Ca-v alpha 1). These loops interact with target proteins in a Ca2+-dependent or independent manner. In Ca(v)2.3- containing channels the cytosolic linker between domains II and III confers a novel Ca2+ sensitivity to E-type Ca2+ channels including phorbol ester sensitive signalling via protein kinase C ( PKC) in Ca(v)2.3 transfected HEK-293 cells. To understand Ca2+ and phorbol ester mediated activation of Ca(v)2.3 Ca2+ channels, protein interaction partners of the II-III loop were identified. FLAG-tagged II-III-loop of human Ca(v)2.3 was over-expressed in HEK 293 cells, and the molecular chaperone hsp70, which is known to interact with PKC, was identified as a novel functional interaction partner. Immunopurified II-III loop-protein of neuronal and endocrine Ca(v)2.3 splice variants stimulate autophosphorylation of PKC alpha, leading to the suggestion that hsp70-binding to the II-III loop-may act as an adaptor for Ca2+ dependent targeting of PKC to E-type Ca2+ channels.
引用
收藏
页码:97 / 110
页数:14
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