Microtubule Detyrosination Drives Symmetry-Breaking to Polarize Cells for Directed Cell Migration

• DOI: 10.2139/ssrn.4156165
• Publication Date: 2022-07-14T19:25:42Z
• Authors: Kirstine Lavrsen; Girish Rajendrapr...; Marcin Leda; Susana Eibes; Elisa Vitiello; Vasileios Katopodis; Andrew Goryachev; Marin Barisic
• Keywords: microtubules; cell polarity; cell migration; Cell Movement; tubulin code; Kinesins; Biological Sciences; Microtubules; kinesins; Cytoskeleton

To initiate directed movement, cells must become polarized, establishing a protrusive leading edge and contractile trailing edge. This symmetry-breaking process involves reorganization of cytoskeleton asymmetric distribution regulatory molecules. However, what triggers maintains this asymmetry during cell migration remains largely elusive. Here, we established micropatterning-based 1D motility assay to investigate the molecular basis required for migration. We show that microtubule detyrosination drives polarization by directing kinesin-1-based transport adenomatous polyposis coli (APC) protein cortical sites. is essential formation cell´s 3D These data, combined with biophysical modeling, unveil key role in generation positive feedback loop linking dynamics transport. Thus, relies on driven supports migration.Funding Information: Work lab MB supported grants from Danish Cancer Society (R146-A9322), Lundbeck Foundation (R215-2015-4081) Novo Nordisk (NNF19OC0058504). ABG Biotechnology Biological Sciences Research Council (BB/P01190X BB/P006507).Conflict Interests: The authors declare no competing interests.