TY - JOUR
T1 - Septin-microtubule association via a motif unique to isoform 1 of septin 9 tunes stress fibers
AU - Kuzmić, Mira
AU - Castro Linares, Gerard
AU - Leischner Fialová, Jindřiška
AU - Iv, François
AU - Salaün, Danièle
AU - Llewellyn, Alex
AU - Gomes, Maxime
AU - Belhabib, Mayssa
AU - Koenderink, Gijsje H.
AU - More Authors, null
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Actin
KW - Cytoskeleton
KW - Microtubule
KW - SEPT9
KW - Septin
UR - http://www.scopus.com/inward/record.url?scp=85123391108&partnerID=8YFLogxK
U2 - 10.1242/jcs.258850
DO - 10.1242/jcs.258850
M3 - Article
C2 - 34854883
AN - SCOPUS:85123391108
SN - 0021-9533
VL - 135
JO - Journal of cell science
JF - Journal of cell science
IS - 1
M1 - jcs258850
ER -