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Author Notes:

Address correspondence to Andrew P. Kowalczyk, Dept. of Dermatology, Woodruff Memorial Building, Rm. 5007, Emory University School of Medicine, 1639 Pierce Dr., Atlanta, GA 30322. Tel.: (404) 727-8517. Fax: (404) 727-5878. email: akowalc@emory.edu

We acknowledge Dr. S. LaFlamme for providing cDNA reagents, and Drs. M. Powers and K.J. Green for helpful comments and suggestions.

We gratefully acknowledge Dr. A. Reynolds for providing cDNA reagents. Special thanks to S. Summers for assistance with adenoviral reagents.

Subjects:

Research Funding:

This work was supported by the American Cancer Society (RPG CSM-100348), American Heart Association (AHA) (0355293B), and by National Institutes of Health grants (1R01AR048266 and P30AR042687). K. Xiao was supported by an AHA fellowship.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • adhesion
  • cytoskeleton
  • endocytosis
  • cadherin
  • catenin
  • BETA-CATENIN
  • VE-CADHERIN
  • ADHERENS JUNCTIONS
  • INTERMEDIATE FILAMENTS
  • TUMOR PROGRESSION
  • ARMADILLO FAMILY
  • BARRIER FUNCTION
  • ADHESION SYSTEM
  • ENDOCYTOSIS
  • PROTEIN

Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells

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Journal Title:

Journal of Cell Biology

Volume:

Volume 163, Number 3

Publisher:

, Pages 535-545

Type of Work:

Article | Final Publisher PDF

Abstract:

The mechanisms by which catenins regulate cadherin function are not fully understood, and the precise function of p120 catenin (p120ctn) has remained particularly elusive. In microvascular endothelial cells, p120ctn colocalized extensively with cell surface VE-cadherin, but failed to colocalize with VE-cadherin that had entered intracellular degradative compartments. To test the possibility that p120ctn binding to VE-cadherin regulates VE-cadherin internalization, a series of approaches were undertaken to manipulate p120ctn availability to endogenous VE-cadherin. Expression of VE-cadherin mutants that competed for p120ctn binding triggered the degradation of endogenous VE-cadherin. Similarly, reducing levels of p120ctn using siRNA caused a dramatic and dose-related reduction in cellular levels of VE-cadherin. In contrast, overexpression of p120ctn increased VE-cadherin cell surface levels and inhibited entry of cell surface VE-cadherin into degradative compartments. These results demonstrate that cellular levels of p120ctn function as a set point mechanism that regulates cadherin expression levels, and that a major function of p120ctn is to control cadherin internalization and degradation.

Copyright information:

© 2003, The Rockefeller University Press

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-nc-sa/4.0/).

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