Ca<sup>2+</sup> as a coordinator of skeletal muscle differentiation, fusion and contraction

Sinha, Sansrity; Elbaz‐Alon, Yael; Avinoam, Ori

doi:10.1111/febs.16552

Cited by 11 publications

(7 citation statements)

References 139 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Physiologically, STAC3 oversees the biochemical relationship between calcium sensing (DHPR) and calcium-releasing (RYR1) receptors at the sarcoplasmic reticulum in skeletal muscle 23,46 , with calcium homeostasis being essential for active contractions, tissue formation, maturation, and regeneration 65 . In the present work, stac3 -/larvae were found to have lower concentrations of calcium and upregulation of ryr1a in an early patterning of skeletal muscle fibers.…”

Section: Discussionmentioning

confidence: 99%

Early life lipid overload in Native American myopathy is phenocopied by stac3 knock out in zebrafish

Donaka

Zheng

Karasik

2023

Preprint

View full text Add to dashboard Cite

Understanding the early stages of human congenital myopathies is critical for proposing strategies for improving skeletal muscle performance by restoring the functional integrity of cytoskeleton. SH3 and cysteine-rich domain 3 (Stac3) is a protein involved in nutrient sensing, and is an essential component of the excitation-contraction (EC) coupling machinery for Ca2+ releasing. A mutation in STAC3 causes debilitating Native American myopathy (NAM) in humans, and loss of this gene in mice and zebrafish resulted in death in early life. Previously, NAM patients demonstrated increased lipids in skeletal muscle biopsy. However, whether elevated neutral lipids could alter muscle function in NAM disease is now well understood. Here, using a CRISPR/Cas9 induced stac3 knockout (KO) zebrafish model, we determined that loss of stac3 led to muscle weakness, as evidenced by delayed larval hatching. We observed decreased whole-body Ca2+ level at 5 days post-fertilization (dpf) and defects in the skeletal muscle cytoskeleton, i.e., F-actin and slow muscle fibers at 5 and 7 dpf. To this end, myogenesis regulators such as myoD and myf5, were significantly altered in stac3−/− larvae at 5 dpf. Homozygous larvae exhibited elevated neutral lipid levels at 5 dpf, which persisted beyond 7 dpf, followed by a progressive demise of the KO larva by 11 dpf. In summary, the presented findings suggest that stac3−/− can serve as a non-mammalian model to identify lipid-lowering molecules for refining muscle function in NAM patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Early life lipid overload in Native American myopathy is phenocopied by stac3 knock out in zebrafish

Donaka

Zheng

Karasik

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Physiologically, STAC3 oversees the biochemical relationship between calcium sensing (DHPR) and calcium-releasing (RYR1) receptors at the sarcoplasmic reticulum in skeletal muscle 20,43 , with calcium homeostasis being essential for active contractions, tissue formation, maturation, and regeneration 62 . In the present work, stac3 -/larvae were found to have lower concentrations of calcium and upregulation of ryr1a in an early patterning of skeletal muscle fibers.…”

Section: Discussionmentioning

confidence: 99%

Early life lipid overload in Native American myopathy is phenocopied bystac3knock out in zebrafish

Donaka¹,

Zheng

Karasik³

2023

Preprint

View full text Add to dashboard Cite

Understanding the early stages of human congenital myopathies is critical for proposing strategies for improving skeletal muscle performance by the functional integrity of cytoskeleton. SH3 and cysteine-rich domain 3 (Stac3) is a protein involved in nutrient sensing, and is an essential component of the excitation-contraction (EC) coupling machinery for Ca2+ releasing. A mutation in STAC3 causes debilitating Native American myopathy (NAM) in humans, and loss of this gene in mice and zebrafish resulted in death in early life. Previously, NAM patients demonstrated increased lipids in skeletal muscle biopsy. However, elevated neutral lipids could alter muscle function in NAM disease via EC coupling apparatus is yet undiscovered in early development. Here, using a CRISPR/Cas9 induced stac3 knockout (KO) zebrafish model, we determined that loss of stac3 led to muscle weakness, as evidenced by delayed larval hatching. We observed decreased whole-body Ca2+ level at 5 days post-fertilization (dpf) and defects in the skeletal 35 muscle cytoskeleton, i.e., F-actin and slow muscle fibers at 5 and 7 dpf. Homozygous larvae 36 exhibited elevated neutral lipid levels at 5 dpf, which persisted beyond 7 dpf. Myogenesis regulators such as myoD and myf5, were significantly altered in stac3-/- larvae at 5 dpf, thus a progressive death of the KO larva by 11 dpf. In summary, the presented findings suggest that stac3-/- can serve as a non-mammalian model to identify lipid-lowering molecules for refining muscle function in NAM patients.

show abstract

“…Particularly, PS that is located in the inner leaflet of the plasma membrane (Balasubramanian & Schroit, 2003) needed to be translocated to the outer leaflet of lipid bilayer to promote fusion of the myoblasts. The subsequent inward translocation of PS by specific phospholipid flippase complex switches on PIEZO1 and allows the entry of Ca 2+ ions that are critical for myotube formation and muscle contraction (Ortuste Quiroga et al, 2022; Sinha et al, 2022; Figure 2). Recently, it was shown that the application of the selective PIEZO1 agonist—Yoda1, leads to PS externalization in red blood cells from patients with sickle cell anemia but, interestingly, external Ca 2+ is not required for PS exposure (Wadud et al, 2020).…”

Section: Regulation Of Piezo1 By Lipidsmentioning

confidence: 99%

Regulation of PIEZO1 channels by lipids and the structural components of extracellular matrix/cell cytoskeleton

Vasileva

Chubinskiy-Nadezhdin

2023

Journal Cellular Physiology

View full text Add to dashboard Cite

PIEZO1 is a mechanosensitive channel widely presented in eukaryotic organisms. Although the PIEZO family was discovered in 2010, main questions related to the molecular structure as well as to specific activation mechanisms and regulating pathways remain open. Two hypotheses of PIEZO1 gating were formulated: the first, as a dominant hypothesis, through the plasma membrane (force‐from‐lipids) and the second, via the participation of the cytoskeleton and the components of the extracellular matrix (ECM) (force‐from‐filaments). Many researchers provide convincing evidence for both hypotheses. It was demonstrated that PIEZO1 has a propeller‐like shape forming a membrane curvature within the lipid bilayer. That suggests the participation of lipids in channel modulation, and many studies demonstrate the critical role of lipids and compounds that modify the lipid bilayer in the regulation of PIEZO1 properties. At the same time, the components of ECM and cortical cytoskeleton can be affected by the membrane curvature and thus have an impact on PIEZO1 properties. In living cells, PIEZO1 properties are reported to be critically dependent on channel microenvironment that is on combinatorial influence of plasma membrane, cytoskeleton and ECM. Thus, it is necessary to understand which factors can affect PIEZO1 and consider them when interpreting the role of PIEZO1 in various physiological processes. This review summarizes the current knowledge about regulation of Piezo1 by lipids and the components of ECM and cytoskeleton.

show abstract

Ca²⁺ as a coordinator of skeletal muscle differentiation, fusion and contraction

Cited by 11 publications

References 139 publications

Early life lipid overload in Native American myopathy is phenocopied by stac3 knock out in zebrafish

Early life lipid overload in Native American myopathy is phenocopied by stac3 knock out in zebrafish

Early life lipid overload in Native American myopathy is phenocopied bystac3knock out in zebrafish

Regulation of PIEZO1 channels by lipids and the structural components of extracellular matrix/cell cytoskeleton

Contact Info

Product

Resources

About

Ca2+ as a coordinator of skeletal muscle differentiation, fusion and contraction

Cited by 11 publications

References 139 publications

Early life lipid overload in Native American myopathy is phenocopied by stac3 knock out in zebrafish

Early life lipid overload in Native American myopathy is phenocopied by stac3 knock out in zebrafish

Early life lipid overload in Native American myopathy is phenocopied bystac3knock out in zebrafish

Regulation of PIEZO1 channels by lipids and the structural components of extracellular matrix/cell cytoskeleton

Contact Info

Product

Resources

About

Ca²⁺ as a coordinator of skeletal muscle differentiation, fusion and contraction