
==== Front
Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

39184068
10.21203/rs.3.rs-4720604/v1
10.21203/rs.3.rs-4720604
preprint
1
Article
INF2-mediated actin polymerization at ER-organelle contacts regulates organelle size and movement
Manor Uri https://orcid.org/0000-0002-9802-1955

Schiavon Cara
Wang Yuning
Feng Jasmine
Garrett Stephanie
Sung Tsung-Chang
Dayn Yelena
Shadel Gerald https://orcid.org/0000-0003-2899-8717

Quintero-Carmona Omar
Wang Chunxin https://orcid.org/0000-0001-6015-6806

Youle Richard J.
16 8 2024
rs.3.rs-4720604https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4720604/v1
nihpp-rs4720604v1.pdf
Abstract

Proper regulation of organelle dynamics and inter-organelle contacts is critical for cellular health and function. Both the endoplasmic reticulum (ER) and actin cytoskeleton are known to regulate organelle dynamics, but how, when, and where these two subcellular components are coordinated to control organelle dynamics remains unclear. Here, we show that ER-associated actin consistently marks mitochondrial, endosomal, and lysosomal fission sites. We also show that actin polymerization by the ER-anchored isoform of the formin protein INF2 is a key regulator of the morphology and mobility of these organelles. Together, our findings establish a mechanism by which INF2-mediated polymerization of ER-associated actin at ER-organelle contacts regulates organelle dynamics.
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