Septin-microtubule association via a motif unique to isoform 1 of septin 9 tunes stress fibers.

Abstract

Septins, a family of GTP-binding proteins that assemble into higher order structures, interface with the membrane, actin filaments and microtubules, and are thus important regulators of cytoarchitecture. Septin 9 (SEPT9), which is frequently overexpressed in tumors and mutated in hereditary neuralgic amyotrophy (HNA), mediates the binding of septins to microtubules, but the molecular determinants of this interaction remained uncertain. We demonstrate that a short microtubule-associated protein (MAP)-like motif unique to SEPT9 isoform 1 (SEPT9_i1) drives septin octamer-microtubule interaction in cells and in vitro reconstitutions. Septin-microtubule association requires polymerizable septin octamers harboring SEPT9_i1. Although outside of the MAP-like motif, HNA mutations abrogate this association, identifying a putative regulatory domain. Removal of this domain from SEPT9_i1 sequesters septins on microtubules, promotes microtubule stability and alters actomyosin fiber distribution and tension. Thus, we identify key molecular determinants and potential regulatory roles of septin-microtubule interaction, paving the way to deciphering the mechanisms underlying septin-associated pathologies. This article has an associated First Person interview with the first author of the paper.

• Authors: Mira Kuzmić, Gerard Castro Linares, Jindřiška Leischner Fialová, François Iv, Danièle Salaün, Alex Llewellyn, Maxime Gomes, Mayssa Belhabib, Yuxiang Liu, Keisuke Asano, Magda Rodrigues, Daniel Isnardon, Taro Tachibana, Gijsje H Koenderink, Ali Badache, Manos Mavrakis, Pascal Verdier-Pinard
• Journal: Journal of cell science (J Cell Sci) Vol. 135 Issue 1 (01 01 2022) ISSN: 1477-9137 [Electronic] England
• PMID: 34854883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. Published by The Company of Biologists Ltd.

Chemical References

• Microtubule-Associated Proteins
• Protein Isoforms
• SEPTIN9 protein, human
• Septins

Topics

• Humans
• Microtubule-Associated Proteins
• Microtubules (metabolism)
• Protein Isoforms (genetics, metabolism)
• Septins (genetics, metabolism)
• Stress Fibers (metabolism)