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

Chun Tu, Cesar F. Ortega-Cava, Paul Winograd, Marissa Jo Stanton, Alagarsamy Lakku Reddi, Ingrid Dodge, Ranjana Arya, Manjari Dimri, Robert J. Clubb, Mayumi Naramura, Kay Uwe Wagner, Vimla Band, Hamid Band

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16107-16112
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number37
DOIs
StatePublished - Sep 14 2010

Keywords

  • Cell migration
  • Endosomal sorting complexes required for transport
  • Focal adhesion
  • Late endosomal trafficking

ASJC Scopus subject areas

  • General

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