Proteolytic Processing of the C Terminus of the α1CSubunit of L-type Calcium Channels and the Role of a Proline-rich Domain in Membrane Tethering of Proteolytic Fragments*

Although most L-type calcium channel α1C subunits isolated from heart or brain are ∼190-kDa proteins that lack ∼50 kDa of the C terminus, the C-terminal domain is present in intact cells. To test the hypothesis that the C terminus is processed but remains functionally associated with the channels, expressed, full-length α1C subunits were cleaved in vitro by chymotrypsin to generate a 190-kDa C-terminal truncated protein and C-terminal fragments of 30–56 kDa. These hydrophilic C-terminal fragments remained membrane-associated. A C-terminal proline-rich domain (PRD) was identified as the mediator of membrane association. The α1C PRD bound to SH3 domains in Src, Lyn, Hck, and the channel β2 subunit. Mutant α1C subunits lacking either ∼50 kDa of the C terminus or the PRD produced increased barium currents through the channels, demonstrating that these domains participate in the previously described (Wei, X., Neely, a., Lacerda, A. E. Olcese, r., Stefani, E., Perez-Reyes, E., and Birnbaumer, L. (1994) J. Biol. Chem. 269, 1635–1640) inhibition of channel function by the C terminus.

• Publication year

  2000

• Venue

  Journal of Biological Chemistry

• Publication date

  2000-03-24

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.275.12.8556PMID 10722694
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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