Title: T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases | Skeletal Muscle | Full Text
Headings: T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases
T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases
Abstract
Introduction
T-tubule plasticity
Morphological aspects of triad biogenesis
Sarcoplasmic reticulum
Transverse tubule
Molecular mechanisms involved in T-tubule biogenesis and triad formation and maintenance
Table 1 Proteins implicated in triad organization, roles and associated human diseasesa
Caveolin 3
Amphiphysin 2 (BIN1)
Dysferlin
Mitsugumins
Junctophilins
Myotubularin
The RyR-DHPR complex
Conclusion
References
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Content: Note the close proximity of T-tubules and terminal cisternae of the sarcoplasmic reticulum (adapted from [ 104 ]; © 2007 by Pearson Education, Inc.). Full size image
A large set of specialized proteins takes part in EC coupling and includes: i) the Dihydhropyridine Receptor (DHPR), a voltage gated calcium channel located on T-tubule membranes [ 1, 2 ], ii) the Ryanodine Receptor (RyR1), a calcium release channel that is localized on the junctional face of SR and appears as "feet" when observed by electron microscopy (Figure 1, left panel) [ 3 ], iii) calcium buffering proteins such as calsequestrin in the lumen of the SR [ 4 ], iv) calcium channel regulators such as calmodulin, FKBP12 and many others [ 5, 6 ], v) Sarco-Endoplasmic Reticulum Calcium ATPase pumps (SERCA), which is indirectly involved in EC coupling via its action in the rapid removal of the cytosolic calcium after fiber shortening to replenish the calcium stores [ 7 ]. Noteworthy, the physical coupling between RyR1 and DHPR occurs specifically in skeletal but not in cardiac muscles and allows the transmission of the signal within 2 ms in skeletal muscles compared to 100 ms in cardiac muscles [ 8 ]. In cardiac myofiber, RyR2-mediated calcium release is induced by extracellular calcium entry via DHPR in a mechanism called calcium-induced calcium release (CICR) [ 8 ]. Moreover, in fibers of small diameter, such as the body muscles of Amphioxus, peripheral couplings between SR and the plasmalemma have similar function to triads. In addition, all differentiating muscle fibers pass through a stage where T-tubules are not present and EC coupling is mediated by such peripheral couplings. In this review, we will focus on the molecular mechanisms underlying T-tubules biogenesis and triad formation specifically in skeletal muscle. Triad defects linked to human monogenic diseases will also be highlighted.