title: αTAT1 controls longitudinal spreading of acetylation marks from open microtubules extremities.
abstract: Acetylation of the lysine 40 of α-tubulin (K40) is a post-translational modification occurring in the lumen of microtubules (MTs) and is controlled by the α-tubulin acetyl-transferase αTAT1. How αTAT1 accesses the lumen and acetylates α-tubulin there has been an open question. Here, we report that acetylation starts at open ends of MTs and progressively spreads longitudinally from there. We observed acetylation marks at the open ends of in vivo MTs re-growing after a Nocodazole block, and acetylated segments growing in length with time. Bias for MTs extremities was even more pronounced when using non-dynamic MTs extracted from HeLa cells. In contrast, K40 acetylation was mostly uniform along the length of MTs reconstituted from purified tubulin in vitro. Quantitative modelling of luminal diffusion of αTAT1 suggested that the uniform acetylation pattern observed in vitro is consistent with defects in the MT lattice providing lateral access to the lumen. Indeed, we observed that in vitro MTs are permeable to macromolecules along their shaft while cellular MTs are not. Our results demonstrate αTAT1 enters the lumen from open extremities and spreads K40 acetylation marks longitudinally along cellular MTs. This mode of tip-directed microtubule acetylation may allow for selective acetylation of subsets of microtubules.
authors.affiliation: Inserm U1170, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ly
authors.affiliation: Inserm U1170, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Elkhatib
authors.affiliation: Inserm U1170, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
authors.forename: Enzo
authors.initials: E
authors.lastname: Bresteau
authors.affiliation: CNRS UMR8126, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Piétrement
authors.affiliation: CNRS UMR1186, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khaled
authors.affiliation: Institut Curie, CNRS UMR3348, PSL Research University, Centre Universitaire, Orsay, France.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Magiera
authors.affiliation: Institut Curie, CNRS UMR3348, PSL Research University, Centre Universitaire, Orsay, France.
authors.forename: Carsten
authors.initials: C
authors.lastname: Janke
authors.affiliation: CNRS UMR8126, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Le Cam
authors.affiliation: Department of Physics and Atmospheric Science, Dalhousie University, Halifax, NS, B3H 4R2, Canada.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Rutenberg
authors.affiliation: Inserm U1170, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Montagnac
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000473:pathology; D015739:Nocodazole / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000235:genetics; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D008868:Microtubule Proteins; D034741:RNA, Small Interfering; D014404:Tubulin; D050257:Tubulin Modulators; D000123:Acetyltransferases; C000627069:ATAT1 protein, human; C049182:alpha-tubulin acetylase; D008239:Lysine; D015739:Nocodazole