title: EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin.
abstract: In epithelia, junction proteins are endocytosed for modulation of cell-cell adhesion and cell polarity. In response to growth factors, the cell-cell adhesion protein E-cadherin is internalized from the cell surface with degradation or recycling as potential fates. However, the cellular machinery involved in cadherin internalization and recycling remains controversial. Here we investigated EGF-induced E-cadherin internalization. EGF stimulation of MCF-7 cells resulted in Rac1-modulated macropinocytosis of the E-cadherin-catenin complex into endosomal compartments that colocalized with EEA1 and the sorting nexin, SNX1. Depletion of cellular SNX1 levels by siRNA resulted in increased intracellular accumulation and turnover of E-cadherin internalized from the cell surface in response to EGF. Moreover, SNX1 was also required for efficient recycling of internalized E-cadherin and re-establishment of epithelial adhesion. Together, these findings demonstrate a role for SNX1 in retrieval of E-cadherin from a degradative endosomal pathway and in membrane trafficking pathways that regulate E-cadherin recycling.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Bryant
authors.forename: Markus C
authors.initials: MC
authors.lastname: Kerr
authors.forename: Luke A
authors.initials: LA
authors.lastname: Hammond
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Joseph
authors.forename: Keith E
authors.initials: KE
authors.lastname: Mostov
authors.forename: Rohan D
authors.initials: RD
authors.lastname: Teasdale
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stow
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D010873:Pinocytosis / Q000187:drug effects / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000502:physiology; D058305:Sorting Nexins; D022161:Transport Vesicles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C513978:SNX1 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D004815:Epidermal Growth Factor; D020830:rac1 GTP-Binding Protein