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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
Published on: October 17, 2014
The metalloprotease meprinbeta processes E-cadherin and weakens intercellular adhesion
Maya Huguenin1, Eliane J Müller, Sandra Trachsel-Rösmann
1Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Plos One
|May 15, 2008
Summary
Meprin beta protease cleaves E-cadherin in epithelial cells, impacting cell adhesion. This finding reveals a new role for meprin beta in controlling cell-cell interactions and may influence cancer progression.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Meprin, an astacin-like metalloprotease, is found in intestinal and kidney epithelial cells.
- Meprin's association with cancer is established, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of meprin alpha and meprin beta in epithelial cells.
- To identify substrates of meprin proteases in a cellular context.
Main Methods:
- Established cell models (MDCK, Caco-2) expressing meprin alpha or beta.
- Analyzed E-cadherin cleavage using Western blotting and identified cleavage sites.
- Utilized purified meprin beta and other proteases (ADAM-10, MMP-7) for in vitro cleavage assays.
- Examined protein localization via confocal microscopy.
Main Results:
- Meprin beta specifically cleaved E-cadherin, generating a 97-kDa cell-associated fragment.
- Cleavage occurred at the extracellular domain near the plasma membrane.
- Meprin beta activity reduced cell-cell contact strength and multicellular aggregate formation.
- Intracellular processing of beta-catenin and plakoglobin was observed.
Conclusions:
- E-cadherin is a novel substrate for meprin beta in epithelial cells.
- Meprin beta plays a significant role in regulating cell adhesion through E-cadherin cleavage.
- This mechanism has potential implications for epithelial barrier function and cancer progression.
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