NBR1 enables autophagy-dependent focal adhesion turnover. Academic Article uri icon

Overview

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

  • Kenific, Candia
  • Stehbens, Samantha J
  • Goldsmith, Juliet
  • Leidal, Andrew M
  • Faure, Nathalie
  • Ye, Jordan
  • Wittmann, Torsten
  • Debnath, Jayanta

publication date

  • February 22, 2016

Research

keywords

  • Autophagy
  • Focal Adhesions
  • Proteins

Identity

PubMed Central ID

  • PMC4772495

Scopus Document Identifier

  • 84960327345

Digital Object Identifier (DOI)

  • 10.1083/jcb.201503075

PubMed ID

  • 26903539

Additional Document Info

volume

  • 212

issue

  • 5