Inside-out signaling promotes dynamic changes in the carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) oligomeric state to control its cell adhesion properties
| Autor: | Christopher M. Yip, Arianna Rath, Aaron Y.K. Ming, Prerna C. Patel, Scott D. Gray-Owen, Charles M. Deber, Jonathan V. Rocheleau, Hannah S. W. Lee |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Amino Acid Motifs Immunoblotting Molecular Sequence Data Protein Tyrosine Phosphatase Non-Receptor Type 11 Plasma protein binding Biology Biochemistry Cell membrane Calmodulin Antigens CD medicine Cell Adhesion Humans Amino Acid Sequence Cell adhesion Molecular Biology Microscopy Confocal Cell adhesion molecule Effector Protein Tyrosine Phosphatase Non-Receptor Type 6 Cell Membrane Cell Biology Transmembrane protein Cell biology Protein Structure Tertiary Transmembrane domain medicine.anatomical_structure src-Family Kinases Mutation Calcium Signal transduction Protein Multimerization Cell Adhesion Molecules HeLa Cells Protein Binding Signal Transduction |
| Zdroj: | Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) can engage in both cis-homophilic (parallel) oligomerization and trans-homophilic (anti-parallel) binding. In this study, we establish that the CEACAM1 transmembrane domain has a propensity to form cis-dimers via the transmembrane-embedded 432GXXXG436 motif and that this basal state is overcome when activated calmodulin binds to the CEACAM1 cytoplasmic domain. Although mutation of the 432GXXXG436 motif reduced CEACAM1 oligomerization, it did not affect surface localization of the receptor or influence CEACAM1-dependent cellular invasion by the pathogenic Neisseria. The mutation did, however, have a striking effect on CEACAM1-dependent cellular aggregation, increasing both the kinetics of cell-cell association and the size of cellular aggregates formed. CEACAM1 association with tyrosine kinase c-Src and tyrosine phosphatases SHP-1 and SHP-2 was not affected by the 432GXXXG436 mutation, consistent with their association with the monomeric form of wild type CEACAM1. Collectively, our results establish that a dynamic oligomer-to-monomer shift in surface-expressed CEACAM1 facilitates trans-homophilic binding and downstream effector signaling. Background: Carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs) engage in intercellular binding and influence cellular growth and differentiation. Results: Calcium-dependent signals cause dissolution of the transmembrane domain-driven basal state CEACAM1 oligomers into monomers that mediate intercellular binding. Conclusion: Regulated switching in CEACAM1 oligomerization controls cell-cell adhesion and downstream effector recruitment. Significance: Inside-out signaling effects CEACAM1-dependent cell adhesion by controlling a reversible dimer-to-monomer transition. |
| Databáze: | OpenAIRE |
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