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Adherens junction regulates cryptic lamellipodia formation for epithelial cell migration.

J Cell Biol. 2020 Oct 05;219(10)
Masayuki Ozawa 1 , Sylvain Hiver 1 , Takaki Yamamoto 2 , Tatsuo Shibata 2 , Srigokul Upadhyayula 3 , Yuko Mimori-Kiyosue 4 , Masatoshi Takeichi 1
Masayuki Ozawa 1 , Sylvain Hiver 1 , Takaki Yamamoto 2 , Tatsuo Shibata 2 , Srigokul Upadhyayula 3 , Yuko Mimori-Kiyosue 4 , Masatoshi Takeichi 1
+ et al

[No authors listed]

Author information
  • 1 Laboratory for Cell Adhesion and Tissue Patterning, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
  • 2 Laboratory for Physical Biology, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
  • 3 Advanced Bioimaging Center, Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA.
  • 4 Laboratory for Molecular and Cellular Dynamics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

摘要


Collective migration of epithelial cells plays crucial roles in various biological processes such as cancer invasion. In migrating epithelial sheets, leader cells form lamellipodia to advance, and follower cells also form similar motile apparatus at cell-cell boundaries, which are called cryptic lamellipodia (c-lamellipodia). Using adenocarcinoma-derived epithelial cells, we investigated how c-lamellipodia form and found that they sporadically grew from around E-cadherin-based adherens junctions (AJs). WAVE and Arp2/3 complexes were localized along the AJs, and silencing them not only interfered with c-lamellipodia formation but also prevented follower cells from trailing the leaders. Disruption of AJs by removing αE-catenin resulted in uncontrolled c-lamellipodia growth, and this was brought about by myosin II activation and the resultant contraction of AJ-associated actomyosin cables. Additional observations indicated that c-lamellipodia tended to grow at mechanically weak sites of the junction. We conclude that AJs not only tie cells together but also support c-lamellipodia formation by recruiting actin regulators, enabling epithelial cells to undergo ordered collective migration. © 2020 Ozawa et al.