Journal
TRAFFIC
Volume 20, Issue 3, Pages 187-201Publisher
WILEY
DOI: 10.1111/tra.12629
Keywords
cell migration; CLIP-170; endocytosis; Met; trafficking
Categories
Funding
- Canadian Institutes of Health Research
- Susan G. Komen for the Cure grant [KG111467]
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Endocytic sorting of activated receptor tyrosine kinases (RTKs), alternating between recycling and degradative processes, controls signal duration, location and surface complement of RTKs. The microtubule (MT) plus-end tracking proteins (+TIPs) play essential roles in various cellular activities including translocation of intracellular cargo. However, mechanisms through which RTKs recycle back to the plasma membrane following internalization in response to ligand remain poorly understood. We report that net outward-directed movement of endocytic vesicles containing the hepatocyte growth factor (HGF) Met RTK, requires recruitment of the +TIP, CLIP-170, as well as the association of CLIP-170 to MT plus-ends. In response to HGF, entry of Met into Rab4-positive endosomes results in Golgi-localized gamma-ear-containing Arf-binding protein 3 (GGA3) and CLIP-170 recruitment to an activated Met RTK complex. We conclude that CLIP-170 co-ordinates the recycling and the transport of Met-positive endocytic vesicles to plus-ends of MTs towards the cell cortex, including the plasma membrane and the lamellipodia, thereby promoting cell migration.
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