1. Cell Biology
  2. Physics of Living Systems

Persistent cell migration emerges from a coupling between protrusion dynamics and polarized trafficking

  1. Kotryna Vaidžiulytė
  2. Anne-Sophie Macé
  3. Aude Battistella
  4. William Beng
  5. Kristine Schauer  Is a corresponding author
  6. Mathieu Coppey  Is a corresponding author
  1. Institut Curie, France
  2. Institut Gustave Roussy, France
https://doi.org/10.7554/eLife.69229
Share this article
Cite this article
  1. Kotryna Vaidžiulytė
  2. Anne-Sophie Macé
  3. Aude Battistella
  4. William Beng
  5. Kristine Schauer
  6. Mathieu Coppey
(2022)
Persistent cell migration emerges from a coupling between protrusion dynamics and polarized trafficking
eLife 11:e69229.
https://doi.org/10.7554/eLife.69229
  2. Download BibTeX
  3. Download .RIS

Abstract

Migrating cells present a variety of paths, from random to highly directional ones. While random movement can be explained by basal intrinsic activity, persistent movement requires stable polarization. Here, we quantitatively address emergence of persistent migration in RPE1 cells over long timescales. By live-cell imaging and dynamic micropatterning, we demonstrate that the Nucleus-Golgi axis aligns with direction of migration leading to efficient cell movement. We show that polarized trafficking is directed towards protrusions with a 20 min delay, and that migration becomes random after disrupting internal cell organization. Eventually, we prove that localized optogenetic Cdc42 activation orients the Nucleus-Golgi axis. Our work suggests that polarized trafficking stabilizes the protrusive activity of the cell, while protrusive activity orients this polarity axis, leading to persistent cell migration. Using a minimal physical model, we show that this feedback is sufficient to recapitulate the quantitative properties of cell migration in the timescale of hours.

Data availability

Source data files with numerical data and Source Code for all the graphs in the figures are provided as a zip supplementary file attached to each figure in this submission. Raw imaging data for all the figures are available in the BioImage Archive repository at https://www.ebi.ac.uk/biostudies/studies/S-BIAD365 with BioStudies accession number S-BIAD365.

The following data sets were generated

Article and author information

Author details

  1. Kotryna Vaidžiulytė

    UMR144 / UMR168, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2114-3612

  2. Anne-Sophie Macé

    CNRS / UMR144, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  3. Aude Battistella

    UMR144 / UMR168, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  4. William Beng

    UMR144 / UMR168, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  5. Kristine Schauer

    Tumor Cell Dynamics Unit, Institut Gustave Roussy, Villejuif, France
    For correspondence
    kristine.schauer@gustaveroussy.fr
    Competing interests
    The authors declare that no competing interests exist.

  6. Mathieu Coppey

    CNRS / UMR168, Institut Curie, Paris, France
    For correspondence
    mathieu.coppey@curie.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8924-3233

Funding

Programme doctoral Interface pour le Vivant

  • Kotryna Vaidžiulytė

Fondation pour la Recherche Médicale (FDT201904008167)

  • Kotryna Vaidžiulytė

Labex CelTisPhyBio (ANR-10-LBX-0038)

  • Kristine Schauer
  • Mathieu Coppey

Labex and Equipex IPGG (ANR-10-NANO0207)

  • Mathieu Coppey

Idex Paris Science et Lettres (ANR-10-IDEX-0001-02 PSL)

  • Kristine Schauer
  • Mathieu Coppey

Centre National de la Recherche Scientifique

  • Kristine Schauer
  • Mathieu Coppey

Institut Curie

  • Kristine Schauer
  • Mathieu Coppey

French National Research Infrastructure France-BioImaging (ANR-10-INBS-04)

  • Anne-Sophie Macé
  • Mathieu Coppey

Institut Convergences Q-life (ANR-17-CONV-0005)

  • Mathieu Coppey

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Vaidžiulytė et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,213
    views
  • 518
    downloads
  • 19
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Kotryna Vaidžiulytė
  2. Anne-Sophie Macé
  3. Aude Battistella
  4. William Beng
  5. Kristine Schauer
  6. Mathieu Coppey
(2022)
Persistent cell migration emerges from a coupling between protrusion dynamics and polarized trafficking
eLife 11:e69229.
https://doi.org/10.7554/eLife.69229

Share this article

https://doi.org/10.7554/eLife.69229

Categories and tags

Research organism

Further reading

    1. Cell Biology

    Myristoylated Neuronal Calcium Sensor-1 captures the preciliary vesicle at distal appendages

    Tomoharu Kanie, Roy Ng ... Peter K Jackson
    Research Article Updated

    The primary cilium is a microtubule-based organelle that cycles through assembly and disassembly. In many cell types, formation of the cilium is initiated by recruitment of preciliary vesicles to the distal appendage of the mother centriole. However, the distal appendage mechanism that directly captures preciliary vesicles is yet to be identified. In an accompanying paper, we show that the distal appendage protein, CEP89, is important for the preciliary vesicle recruitment, but not for other steps of cilium formation (Kanie et al., 2025). The lack of a membrane-binding motif in CEP89 suggests that it may indirectly recruit preciliary vesicles via another binding partner. Here, we identify Neuronal Calcium Sensor-1 (NCS1) as a stoichiometric interactor of CEP89. NCS1 localizes to the position between CEP89 and the centriole-associated vesicle marker, RAB34, at the distal appendage. This localization was completely abolished in CEP89 knockouts, suggesting that CEP89 recruits NCS1 to the distal appendage. Similar to CEP89 knockouts, preciliary vesicle recruitment as well as subsequent cilium formation was perturbed in NCS1 knockout cells. The ability of NCS1 to recruit the preciliary vesicle is dependent on its myristoylation motif and NCS1 knockout cells expressing a myristoylation defective mutant failed to rescue the vesicle recruitment defect despite localizing properly to the centriole. In sum, our analysis reveals the first known mechanism for how the distal appendage recruits the preciliary vesicles.

    1. Cell Biology

    A hierarchical pathway for assembly of the distal appendages that organize primary cilia

    Tomoharu Kanie, Beibei Liu ... Peter K Jackson
    Research Article Updated

    Distal appendages are ninefold symmetric blade-like structures attached to the distal end of the mother centriole. These structures are critical for the formation of the primary cilium, by regulating at least four critical steps: preciliary vesicle recruitment, recruitment and initiation of intraflagellar transport (IFT), and removal of CP110. While specific proteins that localize to the distal appendages have been identified, how exactly each protein functions to achieve the multiple roles of the distal appendages is poorly understood. Here, we comprehensively analyze known and newly discovered distal appendage proteins (CEP83, SCLT1, CEP164, TTBK2, FBF1, CEP89, KIZ, ANKRD26, PIDD1, LRRC45, NCS1, CEP15) for their precise localization, order of recruitment, and their roles in each step of cilia formation. Using CRISPR-Cas9 knockouts, we show that the order of the recruitment of the distal appendage proteins is highly interconnected and a more complex hierarchy. Our analysis highlights two protein modules, CEP83-SCLT1 and CEP164-TTBK2, as critical for structural assembly of distal appendages. Functional assays revealed that CEP89 selectively functions in the RAB34+ vesicle recruitment, while deletion of the integral components, CEP83-SCLT1-CEP164-TTBK2, severely compromised all four steps of cilium formation. Collectively, our analyses provide a more comprehensive view of the organization and the function of the distal appendage, paving the way for molecular understanding of ciliary assembly.

    1. Cell Biology
    2. Medicine

    Pulmonary Hypertension: When cell teamwork turns toxic

    Wadih EI Khoury, Stephen Y Chan
    Insight

    In pulmonary hypertension, a combination of metabolic and mechanical dysfunction leads to irreversible vascular damage.