Molecular determinants of cysteine string protein modulation of N-type calcium channels

Date

2003

Authors

Miller, Linda C.
Swayne, Leigh Anne
Kay, Jason G.
Feng, Zhong-Ping
Jarvis, Scott E.
Zamponi, Gerald W.
Braun, Janice E. A.

Journal Title

Journal ISSN

Volume Title

Publisher

Journal of Cell Science

Abstract

Cysteine string proteins (CSPs) are secretory vesicle chaperones that are important for neurotransmitter release. We have previously reported an interaction of CSP with both heterotrimeric GTP-binding proteins (G proteins) and N-type calcium channels that results in a tonic G protein inhibition of the channels. In this report we directly demonstrate that two separate regions of CSP associate with G proteins. The N-terminal binding site of CSP, which includes the J domain, binds Ga subunits but not Gbg subunits whereas the C terminal binding site of CSP associates with either free Gbg subunits or Gbg in complex with Ga. The interaction of either binding site of CSP (CSP1-82 or CSP83-198) with G proteins elicits robust tonic inhibition of N-type calcium channel activity. However, CSP1-82 inhibition and CSP83-198 inhibition of calcium channels occur through distinct mechanisms. Calcium channel inhibition by CSP83-198 (but not CSP1-82) is completely blocked by co-expression of the synaptic protein interaction site (synprint) of the N-type channel, indicating that CSP83-198 inhibition is dependent on a physical interaction with the calcium channel. These results suggest that distinct binding sites of CSP can play a role in modulating G protein function and G protein inhibition of calcium channels.

Description

Keywords

Cysteine string protein, Chaperones, G proteins, N-type calcium channels, Synaptic transmission, J domain

Citation

Miller, L.C., Swayne, L.A., Kay, J.G., Feng, Z-P., Jarvis, S.E., Zamponi, G.W. & Braun, J.E.A. (2003). Molecular determinants of cysteine string protein modulation of N-type calcium channels. Journal of Cell Science, 116(14), 2967-2974.