Ca2+ tunneling architecture and function are important for secretion.

IF 7.4 1区 生物学 Q1 CELL BIOLOGY
Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-05 DOI:10.1083/jcb.202402107
Raphael J Courjaret, Larry E Wagner, Rahaf R Ammouri, David I Yule, Khaled Machaca
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引用次数: 0

Abstract

Ca2+ tunneling requires both store-operated Ca2+ entry (SOCE) and Ca2+ release from the endoplasmic reticulum (ER). Tunneling expands the SOCE microdomain through Ca2+ uptake by SERCA into the ER lumen where it diffuses and is released via IP3 receptors. In this study, using high-resolution imaging, we outline the spatial remodeling of the tunneling machinery (IP3R1; SERCA; PMCA; and Ano1 as an effector) relative to STIM1 in response to store depletion. We show that these modulators redistribute to distinct subdomains laterally at the plasma membrane (PM) and axially within the cortical ER. To functionally define the role of Ca2+ tunneling, we engineered a Ca2+ tunneling attenuator (CaTAr) that blocks tunneling without affecting Ca2+ release or SOCE. CaTAr inhibits Cl- secretion in sweat gland cells and reduces sweating in vivo in mice, showing that Ca2+ tunneling is important physiologically. Collectively our findings argue that Ca2+ tunneling is a fundamental Ca2+ signaling modality.

Ca2+ 隧道结构和功能对分泌非常重要。
Ca2+ 隧道需要储存操作的 Ca2+ 进入(SOCE)和内质网(ER)的 Ca2+ 释放。隧道效应通过 SERCA 吸收 Ca2+ 进入 ER 管腔扩大 SOCE 微域,Ca2+ 在 ER 管腔扩散并通过 IP3 受体释放。在这项研究中,我们利用高分辨率成像技术,概述了隧道机制(IP3R1、SERCA、PMCA 和作为效应器的 Ano1)相对于 STIM1 的空间重塑对储存耗竭的响应。我们的研究表明,这些调节器在质膜(PM)的横向和皮质 ER 的轴向重新分布到不同的亚域。为了从功能上确定 Ca2+ 隧道的作用,我们设计了一种 Ca2+ 隧道衰减器(CaTAr),它能阻断隧道而不影响 Ca2+ 释放或 SOCE。CaTAr 可抑制汗腺细胞中 Cl- 的分泌,并减少小鼠体内的出汗量,这表明 Ca2+ 隧道在生理上非常重要。总之,我们的研究结果证明 Ca2+ 隧道是一种基本的 Ca2+ 信号传递方式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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