Cylindrical Crystallization of Ca²⁺-ATPase and Its Potential Role in Sarcoplasmic Reticulum Dynamics

How do ryanodine receptors (RyRs) open simultaneously to trigger the contraction of whole myofibrils within a large skeletal muscle cell? One possible answer is the uniformity of mechanosensitive RyRs, which is mechanically forced by the neighboring environment, including proteins. Here, we review papers addressing this proposed "mechanical sarcoplasmic reticulum (SR) paradigm". Crystals of the molecular complexes comprising RyR and L-type voltage-gated Ca²⁺ channels were observed at the T-tubule/SR junction in situ using cryo-electron tomography. Observations of the SR vesicles isolated from rabbit and scallop cross-striated muscles using negative staining and transmission electron microscope raised a hypothesis of dynamic rearrangement of the Ca²⁺-ATPase (ATPase) molecules in response to cytoplasmic calcium concentration, as follows: (i) At a low calcium concentration where the ratio of operating ATPase molecules to the total molecules is at a submaximal level, the ATPase molecules form, at least in part, their cylindrical crystals in the SR membrane with the help of ATP; this results in the elongation of the SR vesicles. (ii) High concentrations of calcium, at which the ratio of operating ATPase molecules is maximal, reversibly collapse the ATPase crystals to transform the elongated vesicles into round forms comprising tightly attached crystal patches. These data further lead to the idea that the reversible growth of cylindrical ATPase crystals provides a dynamic crystalline network, which acts as an "SR membrane-endoskeletal motor" to manipulate the SR movement. The possibility of interactions between ATPase crystals and neighboring RyR crystals is also discussed.