1. Zona occludens proteins modulate podosome formation and function
- Author
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Christiane Wiesner, Tobias B. Huber, Elisabeth Génot, Stefan Linder, Joachim Kremerskothen, Edith Reuzeau, Miriam Stölting, Vanessa van Vliet, Hermann Pavenstädt, Patricia Rottiers, and Adelheid Korb-Pap
- Subjects
Podosome ,Myocytes, Smooth Muscle ,Biochemistry ,Focal adhesion ,Extracellular matrix ,Mice ,Cell cortex ,Genetics ,Animals ,Humans ,Amino Acid Sequence ,Cell adhesion ,Molecular Biology ,Actin ,Binding Sites ,biology ,Chemistry ,Membrane Proteins ,3T3 Cells ,Fibroblasts ,Phosphoproteins ,Actins ,Rats ,Cell biology ,Gene Expression Regulation ,Membrane protein ,Zonula Occludens-1 Protein ,biology.protein ,RNA Interference ,Cortactin ,Protein Binding ,Biotechnology - Abstract
Podosomes are highly dynamic structures that are involved in cell adhesion and extracellular matrix remodeling. They present as intracellular columns composed of an actin-rich core region and a surrounding ring-like structure containing focal adhesion proteins, actin binders as well as cell signaling molecules. A key player in podosome biogenesis is the scaffolding protein cortactin, which is thought to control actin assembly at the core region. We show that the zona occludens protein 1 (ZO-1), a pivotal tight junction protein and known binding partner of cortactin, is a component of podosomes. In the smooth muscle cell line A7r5, phorbol ester treatment induced a rapid relocation of ZO-1 from the cell cortex and cytosolic pools toward newly formed podosomes. Podosomal localization was also observed for the known ZO-1-binding proteins l-afadin, α-catenin, and phospho-connexin 43. Truncation studies revealed that the actin-binding domain but not the association with cortactin is necessary for ZO-1 recruitment to podosomes. Moreover, impaired ZO-1 expression leads to significantly reduced podosome formation and concomitant decreased matrix degradation at podosomes. Our findings demonstrate that besides their known function in tight junction assembly and intercellular communication, zona occludens proteins and their binding partners may play a novel role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling.
- Published
- 2010