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Membrane Tension Orchestrates Rear Retraction in Matrix-Directed Cell Migration.

Published version
Peer-reviewed

Type

Article

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Authors

Hetmanski, Joseph HR 
de Belly, Henry 
Busnelli, Ignacio 
Waring, Thomas 
Nair, Roshna V 

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.

Description

Keywords

RhoGTPase, caveolae, cell invasion, cell migration, cytoskeleton, durotaxis, extracellular matrix, membrane tension, Actin Cytoskeleton, Actins, Animals, Caveolae, Cell Line, Tumor, Cell Membrane, Cell Movement, Cell Polarity, Cell Surface Extensions, Cytoskeleton, Cytosol, Extracellular Matrix, Humans, Mice, Protein Kinase C, Pseudopodia, Rats, Signal Transduction, rho-Associated Kinases, rhoA GTP-Binding Protein

Journal Title

Dev Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

51

Publisher

Elsevier BV