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膜联蛋白A7独立于内体分选转运复合体III介导溶酶体修复。

Annexin A7 mediates lysosome repair independently of ESCRT-III.

作者信息

Ebstrup Malene Laage, Sønder Stine Lauritzen, Fogde Ditte Louise, Heitmann Anne Sofie Busk, Dietrich Tiina Naumanen, Dias Catarina, Jäättelä Marja, Maeda Kenji, Nylandsted Jesper

机构信息

Membrane Integrity, Danish Cancer Institute, Copenhagen, Denmark.

Cell Death and Metabolism, Danish Cancer Institute, Copenhagen, Denmark.

出版信息

Front Cell Dev Biol. 2024 Jan 23;11:1211498. doi: 10.3389/fcell.2023.1211498. eCollection 2023.

Abstract

Lysosomes are crucial organelles essential for various cellular processes, and any damage to them can severely compromise cell viability. This study uncovers a previously unrecognized function of the calcium- and phospholipid-binding protein Annexin A7 in lysosome repair, which operates independently of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery. Our research reveals that Annexin A7 plays a role in repairing damaged lysosomes, different from its role in repairing the plasma membrane, where it facilitates repair through the recruitment of ESCRT-III components. Notably, our findings strongly suggest that Annexin A7, like the ESCRT machinery, is dispensable for membrane contact site formation within the newly discovered phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway. Instead, we speculate that Annexin A7 is recruited to damaged lysosomes and promotes repair through its membrane curvature and cross-linking capabilities. Our findings provide new insights into the diverse mechanisms underlying lysosomal membrane repair and highlight the multifunctional role of Annexin A7 in membrane repair.

摘要

溶酶体是各种细胞过程所必需的关键细胞器,对它们的任何损伤都可能严重损害细胞活力。本研究揭示了钙和磷脂结合蛋白膜联蛋白A7在溶酶体修复中的一种以前未被认识的功能,该功能独立于运输所需的内体分选复合物(ESCRT)机制发挥作用。我们的研究表明,膜联蛋白A7在修复受损溶酶体中发挥作用,这与其在修复质膜中的作用不同,在质膜修复中它通过招募ESCRT-III组分来促进修复。值得注意的是,我们的研究结果强烈表明,与ESCRT机制一样,膜联蛋白A7在新发现的磷酸肌醇引发的膜拴系和脂质运输(PITT)途径中对于膜接触位点的形成是可有可无的。相反,我们推测膜联蛋白A7被招募到受损的溶酶体,并通过其膜曲率和交联能力促进修复。我们的研究结果为溶酶体膜修复的多种潜在机制提供了新的见解,并突出了膜联蛋白A7在膜修复中的多功能作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3c/10860759/751493560023/fcell-11-1211498-g001.jpg

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