Publication: A New β Subtype-specific Interaction in α1ASubunit Controls P/Q-type Ca2+ Channel Activation

Présentation

The cytoplasmic b subunit of voltage-dependent calcium channels modulates channel properties in a subtype-specific manner and is important in channel targeting. A high affinity interaction site between the a1 interaction domain (AID) in the I-II cytoplasmic loop of a1 and the b interaction domain (BID) of the b subunit is highly conserved among subunit subtypes. We describe a new subtype-specific interaction (Ss1) between the amino-terminal cytoplasmic domain of a1A (BI-2) and the carboxyl terminus of b4. Like the interaction identified previously (21) between the carboxyl termini of a1A and b4 (Ss2), the affinity of this interaction is lower than AID-BID, suggesting that these are secondary interactions. Ss1 and Ss2 involve overlapping sites on b4 and are competitive, but neither inhibits the interaction with AID. The interaction with the amino terminus of a1 is isoform-dependent, suggesting a role in the specificity of a1-b pairing. Coexpression of b4 in Xenopus oocytes produces a reduced hyperpolarizing shift in the I-V curve of the a1A channel compared with b3 (not exhibiting this interaction). Replacing the amino terminus of a1A with that of a1C abolishes this difference. Our data contribute to our understanding of the molecular organization of calcium channels, providing a functional basis for variation in subunit composition of native P/Qtype channels