학술논문
Cortical dynamics during cell motility are regulated by CRL3(KLHL21) E3 ubiquitin ligase.
Document Type
Academic Journal
Author
Courtheoux T; Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.; Enchev RI; Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.; Lampert F; Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.; Gerez J; Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.; Beck J; Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.; Picotti P; Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.; Sumara I; 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.; Peter M; Institute of Biochemistry, Department of Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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.