EpCAM promotes endosomal modulation of the cortical RhoA zone for epithelial organization
Cécile Gaston,
Simon Beco,
Bryant Doss,
Meng Pan,
Estelle Gauquelin,
Joseph D’Alessandro,
Chwee Teck Lim,
Benoit Ladoux and
Delphine Delacour ()
Additional contact information
Cécile Gaston: Paris Diderot University
Simon Beco: Paris Diderot University
Bryant Doss: Mechanobiology Institute, T-lab
Meng Pan: Mechanobiology Institute, T-lab
Estelle Gauquelin: Paris Diderot University
Joseph D’Alessandro: Paris Diderot University
Chwee Teck Lim: Mechanobiology Institute, T-lab
Benoit Ladoux: Paris Diderot University
Delphine Delacour: Paris Diderot University
Nature Communications, 2021, vol. 12, issue 1, 1-22
Abstract:
Abstract At the basis of cell shape and behavior, the organization of actomyosin and its ability to generate forces are widely studied. However, the precise regulation of this contractile network in space and time is unclear. Here, we study the role of the epithelial-specific protein EpCAM, a contractility modulator, in cell shape and motility. We show that EpCAM is required for stress fiber generation and front-rear polarity acquisition at the single cell level. In fact, EpCAM participates in the remodeling of a transient zone of active RhoA at the cortex of spreading epithelial cells. EpCAM and RhoA route together through the Rab35/EHD1 fast recycling pathway. This endosomal pathway spatially organizes GTP-RhoA to fine tune the activity of actomyosin resulting in polarized cell shape and development of intracellular stiffness and traction forces. Impairment of GTP-RhoA endosomal trafficking either by silencing EpCAM or by expressing Rab35/EHD1 mutants prevents proper myosin-II activity, stress fiber formation and ultimately cell polarization. Collectively, this work shows that the coupling between co-trafficking of EpCAM and RhoA, and actomyosin rearrangement is pivotal for cell spreading, and advances our understanding of how biochemical and mechanical properties promote cell plasticity.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22482-9
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DOI: 10.1038/s41467-021-22482-9
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