Localization and function of L-type calcium channels in skeletal muscle is regulated by junctophilins.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590271
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Shinshu University
• Principal Investigator: NAKADA Tsutomu 信州大学, 学術研究院医学系, 講師 (70452141)
• Co-Investigator(Renkei-kenkyūsha): YAMADA Mitsuhiko 信州大学, 学術研究院医学系, 教授 (10263237) ; KASHIHARA Toshihide 信州大学, 学術研究院医学系, 助教 (20552334) ; SUZUKI Suechika 神奈川大学, 理学部, 教授 (10082174)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Ｌ型カルシウムチャネル / ジャンクトフィリン / 骨格筋

Outline of Final Research Achievements

L-type calcium channels (LTCC) form a signaling complex with ryanodine receptors at the junctional membrane (JM) in skeletal myocytes. Although junctophilins (JPs) are known to contribute to the stabilization of the JM complex by bridging between the plasma membrane and sarcoplasmic reticulum, the roles of JPs on the JM-targeting and function of LTCC are still unclear. To clarify the roles of JPs, we treated C2C12 and GLT myotubes with siRNA against JP1 or JP2. Knockdown of JPs inhibited the proper JM-targeting and function of LTCC in skeletal myocytes. Co-immunoprecipitation study showed that CaV1.1 interacted with JP1 and JP2 in mouse skeletal muscle. Pull down assay with GST-fusion proteins bearing several partial fragments of CaV1.1 revealed that 12 amino acid residues in the proximal C-terminus are necessary for the binding of CaV1.1 and JPs. These results suggested that interaction of this part of CaV1.1 and JPs is important for the proper localization and function of LTCC.

Free Research Field

薬理学，生理学