title: N-Cadherin Regulates Cell Migration Through a Rab5-Dependent Temporal Control of Macropinocytosis.
abstract: Macropinocytosis is a clathrin-independent endocytic pathway implicated in fluid uptake, pathogen invasion and cell migration. During collective cell migration, macropinocytosis occurs primarily at membrane ruffles arising from the leading edges of migrating cells. We report here that N-cadherin (Ncad) regulates the tempo of macropinocytosis and thereby influences wound-induced collective cell migration. Using live-cell and super-resolution imaging techniques, we observed that Ncad formed clusters at the membrane ruffles and macropinosomes. De-clustering of Ncad by an interfering antibody impaired the recruitment of Rab5-an early endosomal marker-to the macropinosomes. Moreover, we demonstrated that Ncad interacts with Rab5, and laser ablation of Ncad caused Rab5 to dissociate from the macropinosomes. Although Rab5 detached from macropinosomes upon the de-clustering of Ncad, the recruitment of late endosomal marker Rab7 occurred earlier. Consequently, both centripetal trafficking of macropinosomes and collective migration were accelerated due to de-clustering of Ncad. Thus, our results suggest that Ncad is involved in the maturation of macropinocytosis through Rab5 recruitment, linking macropinocytosis and cell migration through a novel function of Ncad.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Wen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Jen-Yeu
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.|Institute of Genomics Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chiu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.|Institute of Pharmaceutics, Development Center for Biotechnology, New Taipei City 221, Taiwan.
authors.forename: Mei-Pin
authors.initials: MP
authors.lastname: Wang
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Sue-Ping
authors.initials: SP
authors.lastname: Lee
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.|Institute of Genomics Sciences, National Yang-Ming University, Taipei 112, Taiwan.|Institute of Pharmaceutics, Development Center for Biotechnology, New Taipei City 221, Taiwan.
authors.forename: Chin-Yin
authors.initials: CY
authors.lastname: Tai
mesh_terms: D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D008954:Models, Biological; D010873:Pinocytosis / Q000502:physiology*; D010957:Plasmids; D021381:Protein Transport; D014945:Wound Healing / Q000502:physiology; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D020696:rab5 GTP-Binding Proteins
keywords: N-cadherin; Rab conversion; Rab5; cell adhesion; cell migration; macropinocytosis; wound healing