Mst4 and Ezrin Induce Brush Borders Downstream of the Lkb1/Strad/Mo25 Polarization Complex

• Published in: Developmental cell Vol. 16; no. 4; pp. 551 - 562
• Main Authors: ten Klooster, Jean Paul, Jansen, Marnix, Yuan, Jin, Oorschot, Viola, Begthel, Harry, Di Giacomo, Valeria, Colland, Frédéric, de Koning, John, Maurice, Madelon M., Hornbeck, Peter, Clevers, Hans
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.04.2009; Cell Press
• Subjects: Adaptor Proteins, Vesicular Transport - metabolism; Biological and medical sciences; Calcium-Binding Proteins - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cell Polarity; CELLBIO; Cytoskeletal Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Microvilli - enzymology; Microvilli - ultrastructure; Models, Biological; Molecular and cellular biology; Phosphoproteins - metabolism; Phosphorylation; Protein Binding; Protein Transport; Protein-Serine-Threonine Kinases - metabolism; CELLBIO; Development; Polarization; Brush border
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2009.01.016

The human Lkb1 kinase, encoded by the ortholog of the invertebrate Par4 polarity gene, is mutated in Peutz-Jeghers cancer syndrome. Lkb1 activity requires complex formation with the pseudokinase Strad and the adaptor protein Mo25. The complex can induce complete polarization in a single isolated intestinal epithelial cell. We describe an interaction between Mo25α and a human serine/threonine kinase termed Mst4. A homologous interaction occurs in the yeast Schizosaccharomyces pombe in the control of polar tip growth. Human Mst4 translocates from the Golgi to the subapical membrane compartment upon activation of Lkb1. Inhibition of Mst4 activity inhibits Lkb1-induced brush border formation, whereas other aspects of polarity such as the formation of lateral junctions remain unaffected. As an essential event in brush border formation, Mst4 phosphorylates the regulatory T567 residue of Ezrin. These data define a brush border induction pathway downstream of the Lkb1/Strad/Mo25 polarization complex, yet separate from other polarity events.