Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent endosomal traffic regulates the localization of active Src at focal adhesions

Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16107-12. doi: 10.1073/pnas.1009471107. Epub 2010 Aug 30.


Active Src localization at focal adhesions (FAs) is essential for cell migration. How this pool is linked mechanistically to the large pool of Src at late endosomes (LEs)/lysosomes (LY) is not well understood. Here, we used inducible Tsg101 gene deletion, TSG101 knockdown, and dominant-negative VPS4 expression to demonstrate that the localization of activated cellular Src and viral Src at FAs requires the endosomal-sorting complexes required for transport (ESCRT) pathway. Tsg101 deletion also led to impaired Src-dependent activation of STAT3 and focal adhesion kinase and reduced cell migration. Impairment of the ESCRT pathway or Rab7 function led to the accumulation of active Src at aberrant LE/LY compartments followed by its loss. Analyses using fluorescence recovery after photo-bleaching show that dynamic mobility of Src in endosomes is ESCRT pathway-dependent. These results reveal a critical role for an ESCRT pathway-dependent LE/LY trafficking step in Src function by promoting localization of active Src to FAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Movement
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Endosomes / metabolism*
  • Humans
  • Lysosomes / metabolism
  • Mice
  • Protein Transport
  • Transcription Factors / metabolism
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*


  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Transcription Factors
  • Tsg101 protein
  • src-Family Kinases