Cav2.3 R-type calcium channels: from its discovery to pathogenic de novo CACNA1E variants: a historical perspective

Figures

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  Fig. 1. Alignment of the cytoplasmic parts from the Cav2.3 S6 segments including 11 out of 14 identified disease-causing missense mutations, GenBank L27745.2 (inspired by Fig. 1 and Fig. S3 in Helbig et al., 2018). Note that for the mutants identified in domain II, recombinant studies have shown that the distal part of Cav2.3 is important for the stability of the open state of Cav2.3 [32]. Further, the first evidence for a strong electromechanical coupling between S4–S5 and the S6 of domain II came from a double mutant cycle analysis of the human Cav2.3 confirming the hypothesis that leucine-596 in the IIS4–S5 linker couples strongly to the distal residues in IIS6 (L A I A V D) labelled in bold in this figure [40]. Three out of 30 mutations were located in IS5 (L228P), IIS4-5 (I603L) and IIIS6-IVS1 (G1430N)

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  Fig. 2. Splice variants of Cav2.3 calcium channels. In the carboxyterminal region, 2 splice variants were found, from which BII-2 had a 272-aas-long insertion in the carboxyterminus