Kenific et al. identify a selective autophagy pathway that promotes cell migration by enhancing the turnover of focal adhesions.
Autophagy pathways target cytoplasmic components for degradation by engulfing them in a double-membraned autophagosome and delivering them to lysosomes. Inhibiting autophagy impairs cell migration, but the reasons for this are unclear. Kenific et al. noticed that autophagy-deficient cells had larger focal adhesions than wild-type cells, suggesting that their migration might be slowed because their attachments to the extracellular matrix are more stable.
Live imaging revealed that, indeed, adhesion turnover was slower in the absence of autophagy. In wild-type cells, autophagosomes targeted focal adhesions as they were being disassembled at the cells’ leading edge, engulfing multiple adhesion components such as paxillin and vinculin. Autophagosomes can be selectively targeted to substrates by specific receptor proteins. Kenific et al. knocked down several autophagy receptors and found that autophagosomes weren’t efficiently targeted to focal adhesions in cells lacking the receptor NBR1. Accordingly, these cells showed reduced rates of adhesion turnover and migrated more slowly than wild-type cells.
Overexpressing NBR1, in contrast, enhanced focal adhesion disassembly, an effect that depended on the protein’s autophagosome- and cargo-binding domains. Senior author Jayanta Debnath now wants to identify which focal adhesion proteins are recognized by NBR1 and how this interaction is regulated. He speculates that autophagosomes may be particularly important for turning over long-lived focal adhesions that have grown too large to be disassembled by other mechanisms.