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8.A.110.  The Junctophilin (JP) Family 

Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. They provide a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH1 contributes to the construction of the skeletal muscle triad by linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes.

Close physical association of CaV1.1 L-type calcium channels (LTCCs) at the sarcolemmal junctional membrane (JM) with ryanodine receptors (RyRs) of the sarcoplasmic reticulum (SR) is crucial for excitation-contraction coupling (ECC) in skeletal muscle (Nakada et al. 2018). Junctophilin 1 (JP1) and JP2 stabilize the JM by bridging the sarcolemmal and SR membranes. JPs recruit LTCCs to the JM through physical interaction and ensure robust ECC at triads in skeletal muscle (Barone et al. 2015). Thus, the physical binding between LTCC and a JP is essential for contraction of striated muscles (Nakada and Yamada 2022).


References associated with 8.A.110 family:

Barone, V., D. Randazzo, V. Del Re, V. Sorrentino, and D. Rossi. (2015). Organization of junctional sarcoplasmic reticulum proteins in skeletal muscle fibers. J Muscle Res Cell Motil 36: 501-515. 26374336
Calpena, E., V. López Del Amo, M. Chakraborty, B. Llamusí, R. Artero, C. Espinós, and M.I. Galindo. (2018). The gene is functionally equivalent to its four mammalian counterparts and is a modifier of a Huntingtin poly-Q expansion and the Notch pathway. Dis Model Mech 11:. 29208631
Chan, B.Y.H., A. Roczkowsky, W.J. Cho, M. Poirier, T.Y.T. Lee, Z. Mahmud, and R. Schulz. (2019). Junctophilin-2 is a target of matrix metalloproteinase-2 in myocardial ischemia-reperfusion injury. Basic Res Cardiol 114: 42. 31506724
Hogea, A., S. Shah, F. Jones, C.M. Carver, H. Hao, C. Liang, D. Huang, X. Du, and N. Gamper. (2021). Junctophilin-4 facilitates inflammatory signalling at plasma membrane-endoplasmic reticulum junctions in sensory neurons. J. Physiol. [Epub: Ahead of Print] 33569781
Jiang, M., J. Hu, F.K.H. White, J. Williamson, A.S. Klymchenko, A. Murthy, S.W. Workman, and G.N. Tseng. (2019). -Palmitoylation of junctophilin-2 is critical for its role in tethering the sarcoplasmic reticulum to the plasma membrane. J. Biol. Chem. 294: 13487-13501. 31337710
Nakada, T. and M. Yamada. (2022). [Regulation of localization and function of L-type calcium channels by junctophilins]. Nihon Yakurigaku Zasshi 157: 4-8. 34980811
Nakada, T., T. Kashihara, M. Komatsu, K. Kojima, T. Takeshita, and M. Yamada. (2018). Physical interaction of junctophilin and the Ca1.1 C terminus is crucial for skeletal muscle contraction. Proc. Natl. Acad. Sci. USA 115: 4507-4512. 29632175
Sahu, G., R.M. Wazen, P. Colarusso, S.R.W. Chen, G.W. Zamponi, and R.W. Turner. (2019). Junctophilin Proteins Tether a Cav1-RyR2-KCa3.1 Tripartite Complex to Regulate Excitability. Cell Rep 28: 2427-2442.e6. 31461656