Eur J Neurosci 2020 May 01;519:1900-1913. doi: 10.1111/ejn.14685.

Cav2.1 C-terminal fragments produced in Xenopus laevis oocytes do not modify the channel expression and functional properties.

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The sequence and genomic organization of the CACNA1A gene that encodes the Cav2.1 subunit of both P and Q-type Ca2+ channels are well conserved in mammals. In human, rat and mouse CACNA1A, the use of an alternative acceptor site at the exon 46-47 boundary results in the expression of a long Cav2.1 splice variant. In transfected cells, the long isoform of human Cav2.1 produces a C-terminal fragment, but it is not known whether this fragment affects Cav2.1 expression or functional properties. Here, we cloned the long isoform of rat Cav2.1 (Cav2.1(e47)) and identified a novel variant with a shorter C-terminus (Cav2.1(e47s)) that differs from those previously described in the rat and mouse. When expressed in Xenopus laevis oocytes, Cav2.1(e47) and Cav2.1(e47s) displayed similar functional properties as the short isoform (Cav2.1). We show that Cav2.1 isoforms produced short (CT1) and long (CT1(e47)) C-terminal fragments that interacted in vivo with the auxiliary Cavβ4a subunit. Overexpression of the C-terminal fragments did not affect Cav2.1 expression and functional properties. Furthermore, the functional properties of a Cav2.1 mutant without the C-terminal Cavβ4 binding domain (Cav2.1ΔCT2) were similar to those of Cav2.1 and were not influenced by the co-expression of the missing fragments (CT2 or CT2(e47)). Our results exclude a functional role of the C-terminal fragments in Cav2.1 biophysical properties in an expression system widely used to study this channel.

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Species referenced: Xenopus laevis
Genes referenced: cacna1a cav2


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