Dataset Information

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca²⁺ signals.

ABSTRACT: The endoplasmic reticulum (ER) forms an interconnected network of tubules stretching throughout the cell. Understanding how ER functionality relies on its structural organization is crucial for elucidating cellular vulnerability to ER perturbations, which have been implicated in several neuronal pathologies. One of the key functions of the ER is enabling Ca[Formula: see text] signaling by storing large quantities of this ion and releasing it into the cytoplasm in a spatiotemporally controlled manner. Through a combination of physical modeling and live-cell imaging, we demonstrate that alterations in ER shape significantly impact its ability to support efficient local Ca[Formula: see text] releases, due to hindered transport of luminal content within the ER. Our model reveals that rapid Ca[Formula: see text] release necessitates mobile luminal buffer proteins with moderate binding strength, moving through a well-connected network of ER tubules. These findings provide insight into the functional advantages of normal ER architecture, emphasizing its importance as a kinetically efficient intracellular Ca[Formula: see text] delivery system.

SUBMITTER: Crapart CC

PROVIDER: S-EPMC10990089 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca<sup>2+</sup> signals.

Crapart Cécile C CC Scott Zubenelgenubi C ZC Konno Tasuku T Sharma Aman A Parutto Pierre P Bailey David M D DMD Westrate Laura M LM Avezov Edward E Koslover Elena F EF

Proceedings of the National Academy of Sciences of the United States of America 20240319 13

The endoplasmic reticulum (ER) forms an interconnected network of tubules stretching throughout the cell. Understanding how ER functionality relies on its structural organization is crucial for elucidating cellular vulnerability to ER perturbations, which have been implicated in several neuronal pathologies. One of the key functions of the ER is enabling Ca[Formula: see text] signaling by storing large quantities of this ion and releasing it into the cytoplasm in a spatiotemporally controlled ma ...[more]

PMID: 38502705

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Project description:Nuclear Ca(2+) is important for the regulation of several nuclear processes such as gene expression. Localized Ca(2+) signals (LCSs) in skeletal muscle fibers of mice have been mainly studied as Ca(2+) release events from the sarcoplasmic reticulum. Their location with regard to cell nuclei has not been investigated. Our study is based on the hypothesis that LCSs associated with nuclei are present in skeletal muscle fibers of adult mice. Therefore, we carried out experiments addressing this question and we found novel Ca(2+) signals associated with nuclei of skeletal muscle fibers (with possibly attached satellite cells). We measured localized nuclear and perinuclear Ca(2+) signals (NLCSs and PLCSs) alongside cytosolic localized Ca(2+) signals (CLCSs) during a hypertonic treatment. We also observed NLCSs under isotonic conditions. The NLCSs and PLCSs are Ca(2+) signals in the range of micrometer [FWHM (full width at half maximum): 2.75 ± 0.27 μm (NLCSs) and 2.55 ± 0.17 μm (PLCSs), S.E.M.]. Additionally, global nuclear Ca(2+) signals (NGCSs) were observed. To investigate which type of Ca(2+) channels contribute to the Ca(2+) signals associated with nuclei in skeletal muscle fibers, we performed measurements with the RyR blocker dantrolene, the DHPR blocker nifedipine or the IP3R blocker Xestospongin C. We observed Ca(2+) signals associated with nuclei in the presence of each blocker. Nifedipine and dantrolene had an inhibitory effect on the fraction of fibers with PLCSs. The situation for the fraction of fibers with NLCSs is more complex indicating that RyR is less important for the generation of NLCSs compared to the generation of PLCSs. The fraction of fibers with NLCSs and PLCSs is not reduced in the presence of Xestospongin C. The localized perinuclear and intranuclear Ca(2+) signals may be a powerful tool for the cell to regulate adaptive processes as gene expression. The intranuclear Ca(2+) signals may be particularly interesting in this respect.

Dataset Information

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca²⁺ signals.

Publications

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca<sup>2+</sup> signals.

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Dataset Information

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca2+ signals.

Publications

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca<sup>2+</sup> signals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca²⁺ signals.