α-tubulin tail modifications regulate microtubule stability through selective effector recruitment, not changes in intrinsic polymer dynamics.

Autor:	Chen J; Cell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA., Kholina E; Department of Biology, Lomonosov Moscow State University, Moscow, Russia., Szyk A; Cell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA., Fedorov VA; Department of Biology, Lomonosov Moscow State University, Moscow, Russia; Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia., Kovalenko I; Department of Biology, Lomonosov Moscow State University, Moscow, Russia; Astrakhan State University, Astrakhan 414056, Russia; Sechenov University, Moscow 119991, Russia., Gudimchuk N; Department of Physics, Lomonosov Moscow State University, Moscow, Russia; Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia; Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Electronic address: nikita_gb@mail.ru., Roll-Mecak A; Cell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA; Biochemistry and Biophysics Center, National Heart Lung and Blood Institute, Bethesda, MD 20892, USA. Electronic address: antonina@mail.nih.gov.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2021 Jul 26; Vol. 56 (14), pp. 2016-2028.e4. Date of Electronic Publication: 2021 May 21.
DOI:	10.1016/j.devcel.2021.05.005
Abstrakt:	Microtubules are non-covalent polymers of αβ-tubulin dimers. Posttranslational processing of the intrinsically disordered C-terminal α-tubulin tail produces detyrosinated and Δ2-tubulin. Although these are widely employed as proxies for stable cellular microtubules, their effect (and of the α-tail) on microtubule dynamics remains uncharacterized. Using recombinant, engineered human tubulins, we now find that neither detyrosinated nor Δ2-tubulin affect microtubule dynamics, while the α-tubulin tail is an inhibitor of microtubule growth. Consistent with the latter, molecular dynamics simulations show the α-tubulin tail transiently occluding the longitudinal microtubule polymerization interface. The marked differential in vivo stabilities of the modified microtubule subpopulations, therefore, must result exclusively from selective effector recruitment. We find that tyrosination quantitatively tunes CLIP-170 density at the growing plus end and that CLIP170 and EB1 synergize to selectively upregulate the dynamicity of tyrosinated microtubules. Modification-dependent recruitment of regulators thereby results in microtubule subpopulations with distinct dynamics, a tenet of the tubulin code hypothesis. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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