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Nature. 2013 Oct 24;502(7472):567-70. doi: 10.1038/nature12571. Epub 2013 Oct 6.

αTAT1 catalyses microtubule acetylation at clathrin-coated pits.

Author information

1
1] Institut Curie, Research Center, 75005 Paris, France [2] Membrane and Cytoskeleton Dynamics, CNRS UMR 144, 75005 Paris, France.

Abstract

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. This subset of stable microtubules accumulates in cell protrusions and regulates cell polarization, migration and invasion. 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, 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.

PMID:
24097348
PMCID:
PMC3970258
DOI:
10.1038/nature12571
[Indexed for MEDLINE]
Free PMC Article

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