Septins are a family of highly conserved small GTP-binding proteins that associate with cell membranes, actin filaments and microtubules, and are increasingly being recognised as central regulators of cell architecture. Of the 13 septins found in mammalian cells, septin 9 (SEPT9) uniquely enables interactions with microtubules, but it has been difficult to define the molecular basis that drives this preferential binding. Here, Gijsje Koenderink, Ali Badache, Manos Mavrakis, Pascal Verdier-Pinard and colleagues (Kuzmić et al., 2022) address this problem by combining functional intracellular studies with in vitro reconstitution assays. The authors show that the binding of septins to microtubules requires a microtubule-associated protein (MAP)-like motif specific to the SEPT9 isoform 1 (SEPT9_i1), and that only septin octamers harbouring this isoform bind specifically to dynamic microtubules and slow down their rate of depolymerisation. The authors also design a number of specific genetic variants that modulate the interaction between microtubules and SEPT9_i1, including mutations similar to those that are frequently found in patients affected by the poorly understood disease hereditary neuralgic amyotrophy. Interestingly, the relocalisation of septin octamers from stress fibres to microtubules causes a proportion of these fibres to be lost from adherent cells and alters their internal tension. These findings shed new light on the molecular determinants of septin association with actin and microtubules, and on their consequences on the organisation of the cytoskeleton.
Newly identified motif explains preferential septin–microtubule association
Newly identified motif explains preferential septin–microtubule association. J Cell Sci 1 January 2022; 135 (1): e135_e0102. doi:
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