| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 104 === Collective cell migration is a prevalent cellular behavior involved in development, tissue repair and tumor invasion. During collective cell migration, the front-raw cells become polarized, which has been suggested to be regulated by macropinocytosis. Macropinocytosis, which occurs primarily at the leading edges of migrating cells, is a clathrin-independent endocytic pathway for fluid uptake or pathogen invasion. Here this thesis reports that N-cadherin, a key component in adherens junctions, has an off-junctional role on regulating the tempo of macropinocytosis, and thereby influences wound-induced collective cell migration. The results of live-cell and super-resolution imaging showed that N-cadherin formed clusters together with Rab5, an early endosome marker, at macropinosomes. Ablation of N-cadherin at macropinosomes impaired Rab5 recruitment, and disruption of N-cadherin clustering hampered the stabilization of Rab5 at macropinosomes and thereby facilitated the recruitment of Rab7, a late-endosome marker, indicating accelerated maturation as well. Consequently, both centripetal trafficking of macropinosomes and collective cell migration were speeded up due to de-clustering of N-cadherin. Hence these results suggested that off-junctional N-cadherin can regulate cell migration via modulating the maturation of macropinosomes through Rab5 recruitment.
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