Late endosomes uproot focal adhesions

Schiefermeier et al. reveal that late endosomes promote cell migration by transporting a signal transduction scaffold complex that stimulates focal adhesion turnover.

p14 and MP1 are two components of an adaptor complex that regulates MAP kinase and mTORC signaling on late endosomes. Schiefermeier et al. noticed that, instead of accumulating in the center of cells like other late endosomes, MP1-positive organelles moved along microtubules toward peripheral focal adhesions attaching the cell to its underlying substrate. In particular, the endosomes targeted the dynamic regions of mature focal adhesions, where adhesion components turn over in order to support cell migration.

The researchers therefore examined fibroblasts lacking p14, in which MP1 is degraded instead of being recruited to late endosomes. These cells developed large, stable focal adhesions and migrated more slowly than control fibroblasts. Knocking down the small GTPase Arl8b, which recruits the motor protein kinesin-1 to late endosomes, abolished the delivery of late endosomes to focal adhesions and caused a similar decrease in adhesion turnover and cell migration.

Schiefermeier et al. found that MP1 binds to the cytoskeletal regulator IQGAP1, a small pool of which localizes to focal adhesions. Excess IQGAP1 accumulated at the enlarged adhesions of fibroblasts lacking p14 or Arl8b. Knocking down IQGAP1 returned adhesions to their normal size and rescued the migration defects of p14-deficient cells.

Late endosomal p14 and MP1 therefore stimulate focal adhesion turnover and cell migration by promoting the removal of IQGAP1 from mature adhesions. Senior author Lukas A. Huber now wants to investigate how this pathway contributes to cancer cell metastasis and wound healing.