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

Meng-Hsuan Wen1,2, Jen-Yeu Wang2, Yu-Ting Chiu2,3

  • 1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.

Traffic (Copenhagen, Denmark)
|April 11, 2016
PubMed

Insights

N-cadherin regulates macropinocytosis speed during collective cell migration. Disrupting N-cadherin accelerates macropinosome trafficking and cell movement by altering Rab5 recruitment.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Macropinocytosis is a clathrin-independent endocytic process crucial for fluid uptake, pathogen entry, and cell motility.
  • During collective cell migration, macropinocytosis is prominent at the leading edges of cells within membrane ruffles.

Purpose of the Study:

  • To investigate the role of N-cadherin (Ncad) in regulating macropinocytosis during collective cell migration.
  • To elucidate the molecular mechanisms by which Ncad influences macropinosome trafficking and cell movement.

Main Methods:

  • Live-cell imaging and super-resolution microscopy to visualize Ncad dynamics at membrane ruffles and macropinosomes.
  • Functional assays using interfering antibodies to de-cluster Ncad.
  • Laser ablation techniques to study Ncad-Rab5 interactions.
  • Immunofluorescence to track endosomal markers (Rab5, Rab7).

Main Results:

  • N-cadherin forms clusters at membrane ruffles and macropinosomes during collective cell migration.
  • De-clustering of Ncad impairs Rab5 recruitment to macropinosomes, indicating a role in early endosomal maturation.
  • Ncad directly interacts with Rab5; its dissociation leads to Rab5 detachment.
  • While Rab5 detaches, Rab7 recruitment is accelerated, speeding up macropinosome trafficking and collective cell migration.

Conclusions:

  • N-cadherin plays a critical role in modulating the kinetics of macropinocytosis through Rab5 recruitment.
  • This study reveals a novel function of N-cadherin in linking macropinocytosis maturation to collective cell migration dynamics.
Keywords:
N-cadherinRab conversionRab5cell adhesioncell migrationmacropinocytosiswound healing

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