RRC ID 43296
著者 Kon S, Tanabe K, Watanabe T, Sabe H, Satake M.
タイトル Clathrin dependent endocytosis of E-cadherin is regulated by the Arf6GAP isoform SMAP1.
ジャーナル Exp Cell Res
Abstract E-cadherin is a central component of the adherens junction in epithelial cells and continuously undergoes endocytosis via clathrin-coated vesicles and/or caveolae depending on the cell type. In this study, we examined the role of SMAP1, a clathrin-interacting GTPase-activating protein (GAP) for the ADP-ribosylation factor 6 (Arf6) GTPase, in E-cadherin endocytosis. Mardin-Darby canine kidney (MDCK) epithelial cells were used as a model, and SMAP1 localized in the cytoplasm and along the adherens junction where E-cadherin was present. Next, activity of SMAP1 was compared with that of other Arf6GAPs (and/or an effector of Arf6-GTP), namely GIT1 and AMAP2/DDEF2. Overexpression of SMAP1 but not GIT1 nor AMAP2/DDEF2 strongly inhibited basal, as well as phorbolester-induced, internalization of E-cadherin. Notably, AMAP2/DDEF2 rather enhanced the caveolae-mediated incorporation of a membrane protein other than E-cadherin. Thus, in MDCK cells, E-cadherin appeared to be endocytosed solely through SMAP1-regulated clathrin-coated vesicles. Furthermore, MDCK cells overexpressing SMAP1 showed a reduced degree of cell migration compared to untransfected cells, as assessed by wound healing and Transwell assays, and this reduction in migration appeared to be due to the accumulation of E-cadherin at the adherens junction in cells overexpressing SMAP1. Collectively, SMAP1 likely represents a key Arf6GAP in clathrin dependent endocytosis of E-cadherin in MDCK cells. This activity of SMAP1 in E-cadherin turnover may be involved in epithelial organization and/or epithelial-mesenchymal transition.
巻・号 314(7)
ページ 1415-28
公開日 2008-4-15
DOI 10.1016/j.yexcr.2007.11.006
PII S0014-4827(07)00526-5
PMID 18331728
MeSH ADP-Ribosylation Factor 6 ADP-Ribosylation Factors / metabolism* Amino Acid Sequence Animals Biotinylation Cadherins / metabolism* Caveolins / metabolism Cell Movement Clathrin / metabolism* Dogs Endocytosis* Epithelium / metabolism GTPase-Activating Proteins / metabolism* Membrane Proteins / chemistry Membrane Proteins / metabolism* Mesoderm / metabolism Mice Molecular Sequence Data Protein Isoforms / metabolism Protein Transport Serum Albumin, Bovine / metabolism Wound Healing
IF 3.383
引用数 32
WOS 分野 ONCOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 MDCK(RCB0995)