JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

Determinants of the voltage dependence of G protein modulation within calcium channel beta subunits.

CaVbeta subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gbetagamma-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVbeta subunit with the CaValpha1 subunit, when such interaction was prevented by a mutation in the alpha1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984-6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVbeta subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVbeta subunit that is required for this process. We have coexpressed the CaVbeta subunit constructs with CaV2.2 and alpha2delta-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVbeta subunit GK domains, from either beta1b or beta2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from beta2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gbetagamma binding affinity, leading to greater tonic modulation by basal levels of Gbetagamma. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVbeta subunit GK domains alone.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app