title: NBR1 enables autophagy-dependent focal adhesion turnover.
abstract: Autophagy is a catabolic pathway involving the sequestration of cellular contents into a double-membrane vesicle, the autophagosome. Although recent studies have demonstrated that autophagy supports cell migration, the underlying mechanisms remain unknown. Using live-cell imaging, we uncover that autophagy promotes optimal migratory rate and facilitates the dynamic assembly and disassembly of cell-matrix focal adhesions (FAs), which is essential for efficient motility. Additionally, our studies reveal that autophagosomes associate with FAs primarily during disassembly, suggesting autophagy locally facilitates the destabilization of cell-matrix contact sites. Furthermore, we identify the selective autophagy cargo receptor neighbor of BRCA1 (NBR1) as a key mediator of autophagy-dependent FA remodeling. NBR1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs, whereas ectopic expression of autophagy-competent, but not autophagy-defective, NBR1 enhances FA disassembly and reduces FA lifetime during migration. Our findings provide mechanistic insight into how autophagy promotes migration by revealing a requirement for NBR1-mediated selective autophagy in enabling FA disassembly in motile cells.
authors.affiliation: Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143 Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Candia M
authors.initials: CM
authors.lastname: Kenific
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Stehbens
authors.affiliation: Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143 Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Juliet
authors.initials: J
authors.lastname: Goldsmith
authors.affiliation: Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Leidal
authors.affiliation: Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faure
authors.affiliation: Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Jordan
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Torsten
authors.initials: T
authors.lastname: Wittmann
authors.affiliation: Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143 Jayanta.Debnath@ucsf.edu.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Debnath
mesh_terms: D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D022001:Focal Adhesions; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C549756:NBR1 protein, human; D011506:Proteins