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The Molecular Chaperone hsp70 Interacts with the Cytosolic II-III Loop of the Cav2.3 E-type Voltagegated Ca2+ Channel

2006; Karger Publishers; Volume: 17; Issue: 3-4 Linguagem: Inglês

10.1159/000092071

1421-9778

Andreas Krieger, Kayalvizhi Radhakrishnan, Alexey Pereverzev, Siarhei A. Siapich, Mohammed Banat, Marcel A. Kamp, Jérôme Leroy, Udo Klöckner, Jürgen Hescheler, Marco Weiergräber, Toni Schneider,

Ion channel regulation and function

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.