Mechanisms of microtubule dynamics and force generation examined with computational modeling and electron cryotomography.

Autor: Gudimchuk NB; Department of Physics, Lomonosov Moscow State University, Moscow, Russia. nikita_gb@mail.ru.; Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia. nikita_gb@mail.ru.; Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. nikita_gb@mail.ru., Ulyanov EV; Department of Physics, Lomonosov Moscow State University, Moscow, Russia., O'Toole E; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA., Page CL; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA., Vinogradov DS; Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia., Morgan G; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA., Li G; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA., Moore JK; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA., Szczesna E; Cell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA., Roll-Mecak A; Cell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA., Ataullakhanov FI; 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., Richard McIntosh J; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Jul 28; Vol. 11 (1), pp. 3765. Date of Electronic Publication: 2020 Jul 28.
DOI: 10.1038/s41467-020-17553-2
Abstrakt: Microtubules are dynamic tubulin polymers responsible for many cellular processes, including the capture and segregation of chromosomes during mitosis. In contrast to textbook models of tubulin self-assembly, we have recently demonstrated that microtubules elongate by addition of bent guanosine triphosphate tubulin to the tips of curving protofilaments. Here we explore this mechanism of microtubule growth using Brownian dynamics modeling and electron cryotomography. The previously described flaring shapes of growing microtubule tips are remarkably consistent under various assembly conditions, including different tubulin concentrations, the presence or absence of a polymerization catalyst or tubulin-binding drugs. Simulations indicate that development of substantial forces during microtubule growth and shortening requires a high activation energy barrier in lateral tubulin-tubulin interactions. Modeling offers a mechanism to explain kinetochore coupling to growing microtubule tips under assisting force, and it predicts a load-dependent acceleration of microtubule assembly, providing a role for the flared morphology of growing microtubule ends.
Databáze: MEDLINE
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