CSN5/Jab1 binds to L-type Ca²⁺ channels and inhibits the Ca²⁺ current

Abstract

The L-type Ca²⁺ channels have a wide tissue distribution and play essential roles in physiological responses. Reguration of L-type Ca²⁺ channels involves the assembly of macromolecular signaling complexes. To find out new molecule involved in the L-type Ca²⁺ channels modulation, we used the intracellular II-III linker of the α_1C subunit of the L-type Ca²⁺ channel as a bait in the yeast two-hybrid system to screen a human heart cDNA library. We identified clones encoding sequence of human COP9 signalosome subunit 5(CSN5)/Jun activation domain-binding protein1(Jab1). The α_1C subunit and CSN5/Jab1 were coimmunoprecipatated in rat heart and colocalaized in sarcolememal membranes and transverse tubules of cardiac myocytes. To examine the effect of CSN5/Jab1 on L-type Ca²⁺ channel activity, patch clamp experiments were performed. Inhibition of endogeneous CSN5/Jab1 expression using siRNA had no effect on voltage-dependent property of Ca²⁺ channels, although the inhibition markedly increased the peak amplitude of the Ca²⁺ current. Our results indicate that CSN5/Jab1 is a protein that plays a newly defined functional role in association with L-type Ca²⁺ channels. [Jpn J Physiol 55 Suppl:S132 (2005)]