Referenced in: none

Automatically associated channels: Cav1.1

Title: The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1.

Authors: Ayuk A Anderson, Xavier Altafaj, Zhenlin Zheng, Zhong-Min Wang, Osvaldo Delbono, Michel Ronjat, Susan Treves, Francesco Zorzato

Journal, date & volume: J. Cell. Sci., 2006 May 15 , 119, 2145-55

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16638807

Abstract
JP-45, an integral protein of the junctional face membrane of the skeletal muscle sarcoplasmic reticulum (SR), colocalizes with its Ca2+ -release channel (the ryanodine receptor), and interacts with calsequestrin and the skeletal-muscle dihydropyridine receptor Cav1. We have identified the domains of JP-45 and the Cav1.1 involved in this interaction, and investigated the functional effect of JP-45. The cytoplasmic domain of JP-45, comprising residues 1-80, interacts with Cav1.1. JP-45 interacts with two distinct and functionally relevant domains of Cav1.1, the I-II loop and the C-terminal region. Interaction between JP-45 and the I-II loop occurs through the alpha-interacting domain in the I-II loop. beta1a, a Cav1 subunit, also interacts with the cytosolic domain of JP-45, and its presence drastically reduces the interaction between JP-45 and the I-II loop. The functional effect of JP-45 on Cav1.1 activity was assessed by investigating charge movement in differentiated C2C12 myotubes after overexpression or depletion of JP-45. Overexpression of JP-45 decreased peak charge-movement and shifted VQ1/2 to a more negative potential (-10 mV). JP-45 depletion decreased both the content of Cav1.1 and peak charge-movements. Our data demonstrate that JP-45 is an important protein for functional expression of voltage-dependent Ca2+ channels.