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

Description

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 a1interaction domain (AID) in the I-II cytoplasmic loop ofa1 and the b interaction domain (BID) of the b subunit ishighly conserved among subunit subtypes. We describea new subtype-specific interaction (Ss1) between theamino-terminal cytoplasmic domain of a1A (BI-2) andthe carboxyl terminus of b4. Like the interaction identified previously (21) between the carboxyl termini of a1Aand b4 (Ss2), the affinity of this interaction is lower thanAID-BID, suggesting that these are secondary interactions. Ss1 and Ss2 involve overlapping sites on b4 andare competitive, but neither inhibits the interactionwith AID. The interaction with the amino terminus of a1is isoform-dependent, suggesting a role in the specificityof a1-b pairing. Coexpression of b4 in Xenopus oocytesproduces a reduced hyperpolarizing shift in the I-Vcurve of the a1A channel compared with b3 (not exhibiting this interaction). Replacing the amino terminus ofa1A with that of a1C abolishes this difference. Our datacontribute to our understanding of the molecular organization of calcium channels, providing a functional basis for variation in subunit composition of native P/Qtype channels

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