αTAT1 catalyses microtubule acetylation at clathrin-coated pits

In eukaryotic cells, a subset of microtubules undergoes acetylation, resulting in stabilization: here, clathrin-coated pits are shown to control microtubule acetylation through a direct interaction between the α-tubulin acetyltransferase αTAT1 and the clathrin adaptor AP2, promoting directional cell migration. Cell motility role for stabilized microtubules A subset of the microtubules in a eukaryotic cell is stabilized by acetylation, but the question of how acetylation is restricted to this microtubule subset has remained unanswered. Here Guillaume Montagnac et al . demonstrate that microtubule acetylation is controlled by clathrin-coated pits (CCPs) through a direct interaction between the α-tubulin acetyltransferase αTAT1 and the clathrin adaptor AP2. This interaction is essential for directional cell migration. This work suggests a role for acetylated microtubule — and an unanticipated role for CCPs — in cell motility. In most eukaryotic cells microtubules undergo post-translational modifications such as acetylation of α-tubulin on lysine 40, a widespread modification restricted to a subset of microtubules that turns over slowly 1 . This subset of stable microtubules accumulates in cell protrusions 2 and regulates cell polarization 3 , migration and invasion 4 , 5 , 6 , 7 . However, mechanisms restricting acetylation to these microtubules are unknown. Here we report that clathrin-coated pits (CCPs) control microtubule acetylation through a direct interaction of the α-tubulin acetyltransferase αTAT1 (refs 8 , 9 ) with the clathrin adaptor AP2. We observe that about one-third of growing microtubule ends contact and pause at CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that αTAT1 localizes to CCPs through a direct interaction with AP2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with CCP accumulation at the leading edge 10 , and interaction of αTAT1 with AP2 is required for directional migration. We conclude that microtubules contacting CCPs become acetylated by αTAT1. In migrating cells, this mechanism ensures the acetylation of microtubules oriented towards the leading edge, thus promoting directional cell locomotion and chemotaxis.