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Traffic. 2016 Jul;17(7):769-85. doi: 10.1111/tra.12402. Epub 2016 May 31.

N-Cadherin Regulates Cell Migration Through a Rab5-Dependent Temporal Control of Macropinocytosis.

Wen MH1,2, Wang JY2, Chiu YT2,3, Wang MP2,4, Lee SP2, Tai CY1,2,3,4.

Author information

1
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
2
Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
3
Institute of Genomics Sciences, National Yang-Ming University, Taipei 112, Taiwan.
4
Institute of Pharmaceutics, Development Center for Biotechnology, New Taipei City 221, Taiwan.

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.

KEYWORDS:

N-cadherin; Rab conversion; Rab5; cell adhesion; cell migration; macropinocytosis; wound healing

PMID:
27062132
DOI:
10.1111/tra.12402
[Indexed for MEDLINE]
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