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PreprintCited by 4Microtubule and mitosis dynamicsCellular Mechanics and InteractionsProtein Kinase Regulation and GTPase Signaling

Optogenetically Induced Microtubule Acetylation Unveils the Molecular Dynamics of Actin-Microtubule Crosstalk in Directed Cell Migration

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Deb Roy, Abhijit, Saez Gonzalez, Cristian, Shahid, Farid, Yadav, Eesha, Inoue, Takanari·2024·The Journal of Cell Biology
DOI 10.1101/2024.12.01.626286PMC PMC11642777
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Abstract

Microtubule acetylation is implicated in regulating cell motility, yet its physiological role in directional migration and the underlying molecular mechanisms have remained unclear. This knowledge gap has persisted primarily due to a lack of tools capable of rapidly manipulating microtubule acetylation in actively migrating cells. To overcome this limitation and elucidate the causal relationship between microtubule acetylation and cell migration, we developed a novel optogenetic actuator, optoTAT, which enables precise and rapid induction of microtubule acetylation within minutes in live cells. Using optoTAT, we observed striking and rapid responses at both molecular and cellular level. First, microtubule acetylation triggers release of the RhoA activator GEF-H1 from sequestration on microtubules. This release subsequently enhances actomyosin contractility and drives focal adhesion maturation. These subcellular processes collectively promote sustained directional cell migration. Our findings position GEF-H1 as a critical molecular responder to microtubule acetylation in the regulation of directed cell migration, revealing a dynamic crosstalk between the actin and microtubule cytoskeletal networks.

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  • Acetylation of Lys40 in α-tubulin facilitates GEFH1 release and activation of the RhoA pathway.

    “acetylation of Lys40 in α-tubulin facilitates GEFH1 release and activation of the RhoA pathway,13”

    From Structural basis of microtubule-mediated signal transduction (2026) · cites this paper as [49]

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Cited by

Sorted by citations

Authors
Deb Roy, A., Saez Gonzalez, C., Shahid, F., Yadav, E., & Inoue, T.
Affiliations
Johns Hopkins University (US)
Corresponding author
Inoue, Takanari
ORCID
Venue
The Journal of Cell Biology
Publisher
openRxiv
Published
2024-12-02
Volume
225
Issue
5
ISSN
0021-9525 (ISSN-L)
DOI
10.1101/2024.12.01.626286
PMC
PMC11642777
OpenAlex
W7138849270
Cited by
4
References
3
Citations by year
2026: 4
FWCI
10.94
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • American Heart Association (23POST1057352)
  • National Institutes of Health
  • National Institute of General Medical Sciences (T32GM007445, R35GM149329, F31GM153141, T32GM144272)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
microtubule acetylation, GEF-H1, cell migration, optogenetic actuators, RhoA activation, actomyosin contractility, focal adhesion maturation, directional migration, cytoskeletal dynamics

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