Open AccessThe Molecular Chaperone hsp70 Interacts with the Cytosolic II-III Loop of the Cav2.3 E-type Voltagegated Ca2+ Channel
Author(s) -
Andreas Krieger,
R. Kanthavel,
Alexey Pereverzev,
Siarhei A. Siapich,
Mohammed Banat,
Marcel A. Kamp,
Jérôme Leroy,
Udo Klöckner,
Jürgen Hescheler,
Marco Weiergräber,
Toni Schneider
Publication year - 2006
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000092071
Subject(s) - hek 293 cells , microbiology and biotechnology , cav1.2 , protein kinase c , cytosol , chaperone (clinical) , voltage gated ion channel , biology , voltage dependent calcium channel , ion channel , chemistry , protein subunit , phosphorylation , biochemistry , calcium , receptor , medicine , organic chemistry , pathology , gene , enzyme
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 (Cava1). These loops interact with target proteins in a Ca2+-dependent or independent manner. In Cav2.3-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 Cav2.3 transfected HEK-293 cells. To understand Ca2+ and phorbol ester mediated activation of Cav2.3 Ca2+ channels, protein interaction partners of the II-III loop were identified. FLAG-tagged II-III - loop of human Cav2.3 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 Cav2.3 splice variants stimulate autophosphorylation of PKCa, 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.