title: Cortical dynamics during cell motility are regulated by CRL3(KLHL21) E3 ubiquitin ligase.
abstract: Directed cell movement involves spatial and temporal regulation of the cortical microtubule (Mt) and actin networks to allow focal adhesions (FAs) to assemble at the cell front and disassemble at the rear. Mts are known to associate with FAs, but the mechanisms coordinating their dynamic interactions remain unknown. Here we show that the CRL3(KLHL21) E3 ubiquitin ligase promotes cell migration by controlling Mt and FA dynamics at the cell cortex. Indeed, KLHL21 localizes to FA structures preferentially at the leading edge, and in complex with Cul3, ubiquitylates EB1 within its microtubule-interacting CH-domain. Cells lacking CRL3(KLHL21) activity or expressing a non-ubiquitylatable EB1 mutant protein are unable to migrate and exhibit strong defects in FA dynamics, lamellipodia formation and cortical plasticity. Our study thus reveals an important mechanism to regulate cortical dynamics during cell migration that involves ubiquitylation of EB1 at focal adhesions.
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Thibault
authors.initials: T
authors.lastname: Courtheoux
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Radoslav I
authors.initials: RI
authors.lastname: Enchev
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lampert
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Juan
authors.initials: J
authors.lastname: Gerez
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Jochen
authors.initials: J
authors.lastname: Beck
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Picotti
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Izabela
authors.initials: I
authors.lastname: Sumara
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C000628126:KLHL21 protein, human; D044767:Ubiquitin-Protein Ligases