Characterization of Post-Translational Modifications to Calsequestrins of Cardiac and Skeletal Muscle
AbstractCalsequestrin is glycosylated and phosphorylated during its transit to its final destination in the junctional sarcoplasmic reticulum. To determine the significance and universal profile of these post-translational modifications to mammalian calsequestrin, we characterized, via mass spectrometry, the glycosylation and phosphorylation of skeletal muscle calsequestrin from cattle (B. taurus), lab mice (M. musculus) and lab rats (R. norvegicus) and cardiac muscle calsequestrin from cattle, lab rats and humans. On average, glycosylation of skeletal calsequestrin consisted of two N-acetylglucosamines and one mannose (GlcNAc2Man1), while cardiac calsequestrin had five additional mannoses (GlcNAc2Man6). Skeletal calsequestrin was not phosphorylated, while the C-terminal tails of cardiac calsequestrin contained between zero to two phosphoryls, indicating that phosphorylation of cardiac calsequestrin may be heterogeneous in vivo. Static light scattering experiments showed that the Ca2+-dependent polymerization capabilities of native bovine skeletal calsequestrin are enhanced, relative to the non-glycosylated, recombinant isoform, which our crystallographic studies suggest may be due to glycosylation providing a dynamic “guiderail”-like scaffold for calsequestrin polymerization. Glycosylation likely increases a polymerization/depolymerization response to changing Ca2+ concentrations, and proper glycosylation, in turn, guarantees both effective Ca2+ storage/buffering of the sarcoplasmic reticulum and localization of calsequestrin (Casq) at its target site. View Full-Text
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Lewis, K.M.; Munske, G.R.; Byrd, S.S.; Kang, J.; Cho, H.-J.; Ríos, E.; Kang, C. Characterization of Post-Translational Modifications to Calsequestrins of Cardiac and Skeletal Muscle. Int. J. Mol. Sci. 2016, 17, 1539.
Lewis KM, Munske GR, Byrd SS, Kang J, Cho H-J, Ríos E, Kang C. Characterization of Post-Translational Modifications to Calsequestrins of Cardiac and Skeletal Muscle. International Journal of Molecular Sciences. 2016; 17(9):1539.Chicago/Turabian Style
Lewis, Kevin M.; Munske, Gerhard R.; Byrd, Samuel S.; Kang, Jeehoon; Cho, Hyun-Jai; Ríos, Eduardo; Kang, ChulHee. 2016. "Characterization of Post-Translational Modifications to Calsequestrins of Cardiac and Skeletal Muscle." Int. J. Mol. Sci. 17, no. 9: 1539.
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