First Author | Tu C | Year | 2010 |
Journal | Proc Natl Acad Sci U S A | Volume | 107 |
Issue | 37 | Pages | 16107-12 |
PubMed ID | 20805499 | Mgi Jnum | J:164362 |
Mgi Id | MGI:4833719 | Doi | 10.1073/pnas.1009471107 |
Citation | Tu C, et al. (2010) 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 107(37):16107-12 |
abstractText | 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. |