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Non-catalytic allostery in α-TAT1 by a phospho-switch drives dynamic microtubule acetylation

Abstract : Spatiotemporally dynamic microtubule acetylation underlies diverse physiological and pathological events. Despite its ubiquity, the molecular mechanisms that regulate the sole microtubule acetylating agent, α-tubulin-N-acetyltransferase-1 (α-TAT1), remain obscure. Here, we report that dynamic intracellular localization of α-TAT1 along with its catalytic activity determines efficiency of microtubule acetylation. Specifically, we newly identified a conserved signal motif in the intrinsically disordered C-terminus of α-TAT1, consisting of three competing regulatory elements—nuclear export, nuclear import, and cytosolic retention. Their balance is tuned via phosphorylation by CDK1, PKA, and CK2, and dephosphorylation by PP2A. While the unphosphorylated form binds to importins and resides both in cytosol and nucleus, the phosphorylated form binds to specific 14-3-3 adapters and accumulates in the cytosol for maximal substrate access. Unlike other molecules with a similar phospho-regulated signal motif, α-TAT1 uniquely uses the nucleus as a hideout. This allosteric spatial regulation of α-TAT1 function may help uncover a spatiotemporal code of microtubule acetylation in normal and aberrant cell behavior.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03831795
Contributor : Marie Lemesle Connect in order to contact the contributor
Submitted on : Thursday, October 27, 2022 - 11:09:48 AM
Last modification on : Thursday, November 3, 2022 - 3:13:31 AM

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Abhijit Deb Roy, Evan G Gross, Gayatri S Pillai, Shailaja Seetharaman, Sandrine Etienne-Manneville, et al.. Non-catalytic allostery in α-TAT1 by a phospho-switch drives dynamic microtubule acetylation. Journal of Cell Biology, 2022, 221 (11), pp.e202202100. ⟨10.1083/jcb.202202100⟩. ⟨pasteur-03831795⟩

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