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Non-junctional Cadherin3 regulates cell migration and contact inhibition of locomotion via domain-dependent opposing regulations of Rac1

View ORCID ProfileTakehiko Ichikawa, Carsten Stuckenholz, View ORCID ProfileLance A. Davidson
doi: https://doi.org/10.1101/750752
Takehiko Ichikawa
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15260, USANano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa 920-1192, Japan
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Carsten Stuckenholz
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15260, USA
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Lance A. Davidson
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15260, USADepartment of Developmental Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USADepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
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  • For correspondence: lance.a.davidson@pitt.edu
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Abstract

Classical cadherins are well-known primary adhesion molecules responsible for physically connecting neighboring cells and signaling the cell-cell contact. Recent studies have suggested novel signaling roles for “non-junctional” cadherins (Niessen and Gottardi, 2008; Padmanabhan et al., 2017); however, the function of cadherin signaling independent of cell-cell contacts remains unknown. In this study, we used mesendoderm cells and tissues from gastrula stage Xenopus laevis embryos to demonstrate that extracellular and cytoplasmic cadherin domains regulate Rac1 in opposing directions in the absence of cell-cell contacts. Furthermore, we found that non-junctional cadherins regulate contact inhibition of locomotion (CIL) during gastrulation through alterations in the stability of the cytoskeleton. Live FRET imaging of Rac1 activity illustrated how non-junction cadherin3 (formerly C-cadherin) spatio-temporally regulates CIL. Our study provides novel insights into adhesion-independent signaling by cadherin3 and its role in regulating single and collective cell migration in vivo.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 29, 2019.
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Non-junctional Cadherin3 regulates cell migration and contact inhibition of locomotion via domain-dependent opposing regulations of Rac1
Takehiko Ichikawa, Carsten Stuckenholz, Lance A. Davidson
bioRxiv 750752; doi: https://doi.org/10.1101/750752
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Non-junctional Cadherin3 regulates cell migration and contact inhibition of locomotion via domain-dependent opposing regulations of Rac1
Takehiko Ichikawa, Carsten Stuckenholz, Lance A. Davidson
bioRxiv 750752; doi: https://doi.org/10.1101/750752

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