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EGF stimulates annexin 1‐dependent inward vesiculation in a multivesicular endosome subpopulation
Author(s) -
White Ian J,
Bailey Lorna M,
Aghakhani Minoo Razi,
Moss Stephen E,
Futter Clare E
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600759
Subject(s) - endosome , escrt , biology , microbiology and biotechnology , annexin a2 , annexin , phosphorylation , endocytic cycle , vacuole , biogenesis , cytoplasm , receptor , endocytosis , biochemistry , flow cytometry , intracellular , gene
Here we show that EGF and EGF receptor (EGFR) are trafficked through a subpopulation of multivesicular endosomes/bodies (MVBs) that are distinct from morphologically identical vacuoles that label for the late endosomal marker lyso‐bisphosphatidic acid (LBPA). EGF stimulation increases both MVB biogenesis and inward vesiculation within EGFR‐containing MVBs. Deletion of annexin 1, a substrate of EGFR tyrosine kinase, abolishes the effect of EGF stimulation on inward vesiculation. This phenotype is reversible by transfection with wild‐type but not Y21F phosphorylation mutant annexin 1. Deletion of annexin 1 has no effect on EGF‐stimulated MVB biogenesis, suggesting that MVB biogenesis and inward vesiculation within MVB are mediated by separate mechanisms. Loss or depletion of annexin 1 has no effect on EGF degradation and causes only a small delay in EGFR degradation, indicating that annexin 1 operates downstream of Hrs‐ and ESCRT‐mediated sorting and is required solely for EGF‐stimulated inward vesiculation. Annexin 1 accumulates on internal vesicles of MVB after EGF‐stimulated inward vesiculation, suggesting that it may be required for a late stage in inward vesiculation.