| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| 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.
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