AHNAK Interaction with the Annexin 2/S100A10 Complex Regulates Cell Membrane Cytoarchitecture

• Published in: The Journal of cell biology Vol. 164; no. 1; pp. 133 - 144
• Main Authors: Benaud, Christelle, Gentil, Benoît J., Assard, Nicole, Court, Magalie, Garin, Jerome, Delphin, Christian, Baudier, Jacques
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 05.01.2004; The Rockefeller University Press
• Subjects: Actin Cytoskeleton - genetics; Actin Cytoskeleton - metabolism; Actins; Animals; Annexin A2 - antagonists & inhibitors; Annexin A2 - genetics; Annexin A2 - metabolism; Annexins; Antibodies; Cell adhesion & migration; Cell Adhesion - genetics; Cell Communication - genetics; Cell Line, Tumor; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cell membranes; Cell Polarity - genetics; Cell Size - genetics; Cells; Cellular biology; Cellular immunity; Cytosol - metabolism; Cytosol - ultrastructure; Dogs; Down-Regulation - genetics; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - ultrastructure; Humans; Intercellular Junctions - metabolism; Intercellular Junctions - ultrastructure; Kidneys; Lipids; Macromolecular Substances; Membrane Proteins - metabolism; Membranes; Neoplasm Proteins - metabolism; Protein Structure, Tertiary - genetics; Rafts; Ribonucleic acid; RNA; RNA, Small Interfering; S100 Proteins - metabolism; Small interfering RNA
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200307098

Remodelling of the plasma membrane cytoarchitecture is crucial for the regulation of epithelial cell adhesion and permeability. In Madin-Darby canine kidney cells, the protein AHNAK relocates from the cytosol to the cytosolic surface of the plasma membrane during the formation of cell-cell contacts and the development of epithelial polarity. This targeting is reversible and regulated by Ca2+-dependent cell-cell adhesion. At the plasma membrane, AHNAK associates as a multimeric complex with actin and the annexin 2/S100A10 complex. The S100A10 subunit serves to mediate the interaction between annexin 2 and the COOH-terminal regulatory domain of AHNAK. Down-regulation of both annexin 2 and S100A10 using an annexin 2-specific small interfering RNA inhibits the association of AHNAK with plasma membrane. In Madin-Darby canine kidney cells, down-regulation of AHNAK using AHNAK-specific small interfering RNA prevents cortical actin cytoskeleton reorganization required to support cell height. We propose that the interaction of AHNAK with the annexin 2/S100A10 regulates cortical actin cytoskeleton organization and cell membrane cytoarchitecture.