1887

Abstract

The yeast gene encodes a homologue of the pore-forming α subunit of mammalian voltage-gated calcium channels. Cch1 cooperates with Mid1, a candidate for a putative, functional homologue of the mammalian regulatory subunit α/δ, and is essential for Ca influx induced by several stimuli. Here, we characterized two mutant alleles of , * (or -star, carrying four point mutations: V49A, N1066D, Y1145H and N1330S) and 2 (formerly designated ). The product of * displayed a marked increase in Ca uptake activity in the presence and absence of α-factor, and its increased activity was still dependent on Mid1. Mutations in * did not affect its susceptibility to regulation by calcineurin. In addition, not only was the N1066D mutation in the cytoplasmic loop between domains II and III responsible for the increased activity of Cch1*, but also substitution of another negatively charged amino acid Glu for Asn resulted in a significant increase in the Ca uptake activity of Cch1. This is the first report of a hyperactive mutation in Cch1. On the other hand, the allele possesses the P1228L mutation located in the extracellular S1–S2 linker of domain III. The Pro residue is highly conserved from fungi to humans, and the P1228L mutation led to a partial loss in Cch1 function, but did not affect the localization and expression of Cch1. The results extend our understanding of the structure–function relationship and functional regulation of Cch1.

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2013-05-01
2019-10-18
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