DOI: 10.1101/493114Dec 11, 2018Paper

Focal adhesion-generated cues in extracellular matrix regulate cell migration by local induction of clathrin-coated plaques

BioRxiv : the Preprint Server for Biology
Delia BucherSteeve Boulant

Abstract

Clathrin is a unique scaffold protein, which forms polyhedral lattices with flat and curved morphology. The function of curved clathrin-coated pits in forming endocytic structures is well studied. On the contrary, the role of large flat clathrin arrays, called clathrin-coated plaques, remains ambiguous. Previous studies suggested an involvement of plaques in cell adhesion. However, the molecular origin leading to their formation and their precise functions remain to be determined. Here, we study the origin and function of clathrin-coated plaques during cell migration. We revealed that plaque formation is intimately linked to extracellular matrix (ECM) modification by focal adhesions (FAs). We show that in migrating cells, FAs digest the ECM creating extracellular topographical cues that dictate the future location of clathrin-coated plaques. We identify Eps15 and Eps15R as key regulators for the formation of clathrin-coated plaques at locally remodelled ECM sites. Using a genetic silencing approach to abrogate plaque formation and 3D-micropatterns to spatially control the location of clathrin-coated plaques, we could directly correlate cell migration directionality with the formation of clathrin-coated plaques and their ability...Continue Reading

Related Concepts

Cell Adhesion
Cell Communication
Extracellular Matrix
Site
Local
Three-dimensional
Location
Extracellular
Genetic Silencer
Clathrin A

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