Membrane Tension Orchestrates Rear Retraction in Matrix-Directed Cell Migration

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2019 Oct 15

PMID 31607653

Citations 69

Authors

Joseph H R Hetmanski

Henry De Belly

Ignacio Busnelli

Thomas Waring

Roshna V Nair

Vanesa Sokleva

Oana Dobre

Angus Cameron

Nils Gauthier

Christophe Lamaze

Joe Swift

Aranzazu Del Campo

Tobias Starborg

Tobias Zech

Jacky G Goetz

Ewa K Paluch

Jean-Marc Schwartz

Patrick T Caswell

Affiliations

Soon will be listed here.

Abstract

In development, wound healing, and cancer metastasis, vertebrate cells move through 3D interstitial matrix, responding to chemical and physical guidance cues. Protrusion at the cell front has been extensively studied, but the retraction phase of the migration cycle is not well understood. Here, we show that fast-moving cells guided by matrix cues establish positive feedback control of rear retraction by sensing membrane tension. We reveal a mechanism of rear retraction in 3D matrix and durotaxis controlled by caveolae, which form in response to low membrane tension at the cell rear. Caveolae activate RhoA-ROCK1/PKN2 signaling via the RhoA guanidine nucleotide exchange factor (GEF) Ect2 to control local F-actin organization and contractility in this subcellular region and promote translocation of the cell rear. A positive feedback loop between cytoskeletal signaling and membrane tension leads to rapid retraction to complete the migration cycle in fast-moving cells, providing directional memory to drive persistent cell migration in complex matrices.

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