Flat clathrin lattices are dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling of specific receptors

Daniela Leyton-Puig, Tadamoto Isogai, Elisabetta Argenzio, Bram van den Broek, Jeffrey Klarenbeek, Hans Janssen, Kees Jalink () and Metello Innocenti ()
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Daniela Leyton-Puig: The Netherlands Cancer Institute
Tadamoto Isogai: The Netherlands Cancer Institute
Elisabetta Argenzio: The Netherlands Cancer Institute
Bram van den Broek: The Netherlands Cancer Institute
Jeffrey Klarenbeek: The Netherlands Cancer Institute
Hans Janssen: The Netherlands Cancer Institute
Kees Jalink: The Netherlands Cancer Institute
Metello Innocenti: The Netherlands Cancer Institute

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Clathrin lattices at the plasma membrane coat both invaginated and flat regions forming clathrin-coated pits and clathrin plaques, respectively. The function and regulation of clathrin-coated pits in endocytosis are well understood but clathrin plaques remain enigmatic nanodomains. Here we use super-resolution microscopy, molecular genetics and cell biology to show that clathrin plaques contain the machinery for clathrin-mediated endocytosis and cell adhesion, and associate with both clathrin-coated pits and filamentous actin. We also find that actin polymerization promoted by N-WASP through the Arp2/3 complex is crucial for the regulation of plaques but not pits. Clathrin plaques oppose cell migration and undergo actin- and N-WASP-dependent disassembly upon activation of LPA receptor 1, but not EGF receptor. Most importantly, plaque disassembly correlates with the endocytosis of LPA receptor 1 and down-modulation of AKT activity. Thus, clathrin plaques serve as dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling that exhibit receptor specificity.

Date: 2017
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DOI: 10.1038/ncomms16068

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