Direct observation of individual tubulin dimers binding to growing microtubules

Proceedings of the National Academy of Sciences of the United States of America
Keith J MickolajczykWilliam O Hancock

Abstract

The biochemical basis of microtubule growth has remained elusive for over 30 years despite being fundamental for both cell division and associated chemotherapy strategies. Here, we combine interferometric scattering microscopy with recombinant tubulin to monitor individual tubulins binding to and dissociating from growing microtubule tips. We make direct, single-molecule measurements of tubulin association and dissociation rates. We detect two populations of transient dwell times and determine via binding-interface mutants that they are distinguished by the formation of one interprotofilament bond. Applying a computational model, we find that slow association kinetics with strong interactions along protofilaments best recapitulate our data and, furthermore, predicts plus-end tapering. Overall, we provide the most direct and complete experimental quantification of how microtubules grow to date.

References

Feb 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·Y D Chen, T L Hill
Apr 1, 1970·Journal of Theoretical Biology·F Oosawa
Nov 15, 1984·Nature·T Mitchison, M Kirschner
Jan 1, 1997·Annual Review of Cell and Developmental Biology·A Desai, T J Mitchison
Dec 4, 1998·Science·H P LuX S Xie
Feb 3, 2000·Journal of the National Cancer Institute·P GiannakakouT Fojo
May 2, 2002·Proceedings of the National Academy of Sciences of the United States of America·Vincent VanBurenLynne Cassimeris
Sep 23, 2003·Protein Science : a Publication of the Protein Society·David SeptJ Andrew McCammon
Apr 2, 2004·Nature Reviews. Cancer·Mary Ann Jordan, Leslie Wilson
Feb 22, 2005·Biophysical Journal·Maxim I MolodtsovFazly I Ataullakhanov
Jun 14, 2005·Biophysical Journal·Vincent VanBurenDavid J Odde
Jun 27, 2006·Nature·Jacob W J KerssemakersMarileen Dogterom
Aug 9, 2007·Current Biology : CB·Henry T SchekAlan J Hunt
Apr 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Luke M RiceDavid A Agard
Jul 16, 2010·Methods in Enzymology·Jeffrey R MoffittCarlos Bustamante
Aug 23, 2011·Cell·Melissa K GardnerDavid J Odde
Sep 22, 2012·Physical Chemistry Chemical Physics : PCCP·Jaime Ortega-Arroyo, Philipp Kukura
Sep 25, 2012·Journal of Structural Biology·Sjors H W Scheres
Mar 28, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hugo Bowne-AndersonJonathon Howard
Jul 9, 2013·Current Biology : CB·Courtney E CoombesMelissa K Gardner
Nov 12, 2014·The Journal of Cell Biology·Gary J Brouhard, Luke M Rice
Oct 7, 2015·Nature Communications·Yalei Chen, William O Hancock
Dec 18, 2015·Proceedings of the National Academy of Sciences of the United States of America·Keith J MickolajczykWilliam O Hancock
Dec 20, 2015·Biophysical Journal·Pavel ZakharovEkaterina L Grishchuk
Apr 30, 2016·The Journal of Biological Chemistry·Annapurna VemuAntonina Roll-Mecak
Nov 5, 2016·Molecular Biology of the Cell·Felipe-Andrés PiedraLuke M Rice
May 18, 2016·The Journal of Cell Biology·Melissa C PamulaTarun M Kapoor
Nov 5, 2016·Molecular Biology of the Cell·Christian DuellbergThomas Surrey
Sep 13, 2016·Nature Cell Biology·Audrey GuesdonDenis Chrétien
Oct 30, 2016·Methods in Enzymology·J AndreckaP Kukura
Mar 3, 2017·Cold Spring Harbor Perspectives in Biology·Hiroaki Ishikawa, Wallace F Marshall
Jun 22, 2017·Biophysical Journal·Keith J Mickolajczyk, William O Hancock
Jun 28, 2017·The Journal of Cell Biology·Stuart C HowesEva Nogales
Jul 12, 2017·Bioscience Reports·Sviatlana Shashkova, Mark C Leake
Oct 11, 2017·Nature Structural & Molecular Biology·Joseph AthertonAnna Akhmanova
Apr 21, 2018·Nature Reviews. Molecular Cell Biology·Gary J Brouhard, Luke M Rice

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Citations

May 1, 2019·Proceedings of the National Academy of Sciences of the United States of America·Valérie CampanacciBenoît Gigant
Aug 20, 2019·The Journal of Cell Biology·Claire StrothmanMarija Zanic
Feb 6, 2020·Molecular Biology of the Cell·Qingzhou FengWilliam O Hancock
Mar 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Nikita Gudimchuk, Antonina Roll-Mecak
Mar 11, 2020·ELife·Juan Estévez-GallegoMaria A Oliva
Feb 13, 2020·Signal Transduction and Targeted Therapy·Zhuoran GongZhifei Dai
Apr 4, 2019·Molecular Biology of the Cell·Tae Kim, Luke M Rice
Feb 6, 2021·The Journal of Cell Biology·Rie AyukawaEtsuko Muto
Apr 17, 2020·Signal Transduction and Targeted Therapy·Zhuoran GongZhifei Dai
May 26, 2021·Current Biology : CB·Joseph M Cleary, William O Hancock
Jun 20, 2021·Nature Communications·Laura SchaedelSarah Köster
Jul 30, 2021·The Journal of Cell Biology·Veronica FarmerMarija Zanic
May 24, 2019·The Journal of Physical Chemistry. B·Lukasz SzatkowskiRuxandra I Dima
Aug 20, 2021·Nature Reviews. Molecular Cell Biology·Nikita B Gudimchuk, J Richard McIntosh
Sep 12, 2019·Chemical Reviews·Gadiel Saper, Henry Hess
Sep 30, 2021·Chemical Reviews·Lee PriestPhilipp Kukura
Dec 18, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ankit RaiAnna Akhmanova

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