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

• 成果类型: Article
• 署名作者: Crapart, Cecile C.; Scott, Zubenelgenubi C.; Konno, Tasuku; Sharma, Aman; Parutto, Pierre; Bailey, David M. D.; Westrate, Laura M.; Avezov, Edward; Koslover, Elena F.
• 署名单位: University of Cambridge; University of Cambridge; University of California System; University of California San Diego; Calvin University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13966
• DOI: 10.1073/pnas.2312172121
• 发表日期: 2024-03-26
• 关键词: inositol trisphosphate; ca2+ release; channel clusters; calcium sparks; elementary; er; diffusion; calreticulin; events; cells

摘要

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 Ca2+ 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 Ca2+ releases, due to hindered transport of luminal content within the ER. Our model reveals that rapid Ca2+ 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 Ca2+ delivery system.