Septins, a family of GTP-binding proteins assembling into higher order structures, interface with the membrane, actin filaments and microtubules, which positions them as 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 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 abrogates 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.
Septin-microtubule association via a motif unique to the isoform 1 of septin 9 tunes stress fibers
Present address: Department of Biology, University of Copenhagen, Copenhagen, Denmark
- Award Group:
- Funder(s): Agence Nationale de la Recherche
- Award Id(s): ANR-17-CE13-0014
- Funder(s):
- Award Group:
- Funder(s): Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Award Id(s): 024.003.019
- Funder(s):
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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; Septin-microtubule association via a motif unique to the isoform 1 of septin 9 tunes stress fibers. J Cell Sci 2021; jcs.258850. doi: https://doi.org/10.1242/jcs.258850
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