Novel Details of Calsequestrin Gel Conformation in Situ

Abstract

Background:Calsequestrin is essential to keep a high calcium concentration inside the sarcoplasmic reticulum of muscle fibers. Results: In situ, calsequestrin polymers appear to form a three-dimensional structure with repeated nodal points. Conclusion: A three-dimensional calsequestrin polymer matrix is very suitable for its spatially confined calcium storage function. Significance: The calsequestrin structure has been extensively studied in ex vivo systems. This approach illustrates the behavior of the protein while still in its physiological cell localization.

Characterization of Two Human Skeletal Calsequestrin Mutants Implicated in Malignant Hyperthermia and Vacuolar Aggregate Myopathy

“…We have interpreted this observation, together with crystallographic studies, as evidence that Casq binds Ca 2ϩ cooperatively, which explains both its greater oligomerization and greater Ca 2ϩ binding capacity as Ca 2ϩ concentrations increase. In vivo, inside the SR, Casq exists in linear ramified polymers, forming a dense network that fills the SR terminal cisternae (6,7). The structure of this network is entirely consistent with the lattice interactions observed in vitro (8).…”

Identification and characterization of three novel mutations in theCASQ1gene in four patients with tubular aggregate myopathy

“…Initial studies with the p.Asp244Gly mutation (Lewis et al., ) indicated that it may decrease the association of dimers through linear back‐to‐back interactions. As shown in Figure D, the p.Ile385Thr mutation is located at the interface of “lateral” back‐to‐back contacts that are responsible for the formation of the branched polymers formed by WT CASQ1 (Perni, Close, & Franzini‐Armstrong, ). Moreover, the negatively charged C‐terminal tail, immediately downstream of Ile385, has been shown to be important to hamper the formation of not‐specific polymerization products (Beard & Dulhunty, ; Park et al., ).…”

Activation and propagation of Ca2+ release from inside the sarcoplasmic reticulum network of mammalian skeletal muscle

“…When the pump cannot balance the leak, CSQ experiences a reduction in its Ca 2+ buffering capacity ( B SR ), probably via depolymerization of its complex structure (Perni et al . ) causing a loss of Ca 2+ ‐binding sites and an increase in [Ca 2+ ] SR follows (Park et al . ; Launikonis et al .…”

“…This leak may be balanced by uptake of Ca 2+ via the SR Ca 2+ pump for a period. When the pump cannot balance the leak, CSQ experiences a reduction in its Ca 2+ buffering capacity (B SR ), probably via depolymerization of its complex structure (Perni et al 2013) causing a loss of Ca 2+ -binding sites and an increase in [Ca 2+ ] SR follows (Park et al 2004;Launikonis et al 2006). This is the intra-SR Ca 2+ transient (Figs 2-12).…”