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PMID:16638807

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Citation

Anderson, AA, Altafaj, X, Zheng, Z, Wang, ZM, Delbono, O, Ronjat, M, Treves, S and Zorzato, F (2006) The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1. J. Cell. Sci. 119:2145-55

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.

Links

PubMed PMC2802288 Online version:10.1242/jcs.02935

Keywords

Animals; Calcium Channels, L-Type/biosynthesis; Calcium Channels, L-Type/metabolism; Calsequestrin/metabolism; Cell Membrane/metabolism; Gene Silencing; Membrane Proteins/biosynthesis; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Muscle, Skeletal/metabolism; Protein Structure, Tertiary; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; Rabbits; Sarcoplasmic Reticulum/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:JSPR1

involved_in

GO:0060314: regulation of ryanodine-sensitive calcium-release channel activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JSPR1

involved_in

GO:0072657: protein localization to membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JSPR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P07293

F

Seeded From UniProt

complete


See also

References

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