Microtubule detyrosination drives symmetry breaking to polarize cells for directed cell migration

Kirstine Lavrsen, Girish Rajendraprasad, Marcin Leda, Susana Eibes, Elisa Vitiello, Vasileios Katopodis, Andrew B. Goryachev, Marin Barisic

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

To initiate directed movement, cells must become polarized, establishing a protrusive leading edge and a contractile trailing edge. This symmetry-breaking process involves reorganization of cytoskeleton and asymmetric distribution of regulatory molecules. However, what triggers and maintains this asymmetry during cell migration remains largely elusive. Here, we established a micropatterning-based 1D motility assay to investigate the molecular basis of symmetry breaking required for directed cell migration. We show that microtubule (MT) detyrosination drives cell polarization by directing kinesin-1-based transport of the adenomatous polyposis coli (APC) protein to cortical sites. This is essential for the formation of cell's leading edge during 1D and 3D cell migration. These data, combined with biophysical modeling, unveil a key role for MT detyrosination in the generation of a positive feedback loop linking MT dynamics and kinesin-1-based transport. Thus, symmetry breaking during cell polarization relies on a feedback loop driven by MT detyrosination that supports directed cell migration.
Original languageEnglish
Article numbere2300322120
Number of pages12
JournalProceedings of the National Academy of Sciences
Issue number22
Early online date22 May 2023
Publication statusPublished - 30 May 2023

Keywords / Materials (for Non-textual outputs)

  • microtubules
  • kinesins
  • tubulin code
  • cell polarity
  • cell migration


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