Channelpedia

PubMed 17950697


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav1.2



Title: Calpastatin binds to a calmodulin-binding site of cardiac Cav1.2 Ca2+ channels.

Authors: Zahangir A Saud, Etsuko Minobe, Wu-yang Wang, Dong-yun Han, Masahisa Horiuchi, Li-Ying Hao, Masaki Kameyama

Journal, date & volume: Biochem. Biophys. Res. Commun., 2007 Dec 14 , 364, 372-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17950697


Abstract
Calpastatin is an endogenous inhibitor of calpain and composed of domain L (CS(L)), which interacts with the Cav1.2 channels, and four repetitive calpain inhibitory domains. We have previously found that CS(L) reprimes activity of the Cav1.2 channels in cell-free patches of cardiac myocytes [L.Y. Hao, A. Kameyama, S. Kuroki, J. Takano, E. Takano, M. Maki, M. Kameyama, Calpastatin domain L is involved in the regulation L-type of Ca2+ channels in guinea pig cardiac myocytes, Biochem. Biophys. Res. Commun. 279 (2000) 756-761; E. Minobe, L.Y. Hao, Z.A. Saud, J.J. Xu, A. Kameyama, M. Maki, K.K. Jewell, T. Parr, R.G. Bardsley, M. Kameyama, A region of calpastatin domain L that reprimes cardiac L-type Ca2+ channels, Biochem. Biophys. Res. Commun. 348 (2006) 288-294]. In this study, we explored the CS(L) interaction site in the Ca2+ channel by the pull-down method, using glutathione-S-transferase-fused fragment peptides of the Cav1.2 channel. CS(L) bound directly to a proximal region of the C-terminal tail of the channel, but not with the N-terminal tail, a distal region of the C-terminal tail or cytoplasmic loops between repeats I-II, II-III or III-IV. Furthermore IQ domain, but not EF-hand-like region or CB domain, in the C-terminal tail was found to bind with CS(L) in a partially Ca2+-dependent manner and in a probably competitive manner with calmodulin. These results suggest that CS(L) modulates Ca2+-channel activity through interacting with the calmodulin-binding site on the C-terminal tail of the Cav1.2 channel.