Engulfed cadherin fingers are polarized junctional structures between collectively migrating endothelial cells

Nat Cell Biol. 2016 Dec;18(12):1311-1323. doi: 10.1038/ncb3438. Epub 2016 Nov 14.

Abstract

The development and maintenance of tissues requires collective cell movement, during which neighbouring cells coordinate the polarity of their migration machineries. Here, we ask how polarity signals are transmitted from one cell to another across symmetrical cadherin junctions, during collective migration. We demonstrate that collectively migrating endothelial cells have polarized VE-cadherin-rich membrane protrusions, 'cadherin fingers', which leading cells extend from their rear and follower cells engulf at their front, thereby generating opposite membrane curvatures and asymmetric recruitment of curvature-sensing proteins. In follower cells, engulfment of cadherin fingers occurs along with the formation of a lamellipodia-like zone with low actomyosin contractility, and requires VE-cadherin/catenin complexes and Arp2/3-driven actin polymerization. Lateral accumulation of cadherin fingers in follower cells precedes turning, and increased actomyosin contractility can initiate cadherin finger extension as well as engulfment by a neighbouring cell, to promote follower behaviour. We propose that cadherin fingers serve as guidance cues that direct collective cell migration.

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism
  • Actomyosin / metabolism
  • Antigens, CD / metabolism*
  • Cadherins / metabolism*
  • Catenins / metabolism
  • Cell Count
  • Cell Membrane / metabolism
  • Cell Movement*
  • Cell Polarity*
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism*
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells / cytology*
  • Humans
  • Imaging, Three-Dimensional
  • Intercellular Junctions / metabolism
  • Mitosis
  • Models, Biological
  • Optogenetics
  • Phagocytosis*
  • Polymerization
  • Pseudopodia / metabolism

Substances

  • Actin-Related Protein 2-3 Complex
  • Antigens, CD
  • Cadherins
  • Catenins
  • cadherin 5
  • Actomyosin