Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex.
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 Mo25alpha 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.
ten Klooster
Jean Paul
JP
Hubrecht Institute, KNAW and University Medical Centre, Utrecht, The Netherlands.
Jansen
Marnix
M
Yuan
Jin
J
Oorschot
Viola
V
Begthel
Harry
H
Di Giacomo
Valeria
V
Colland
Frédéric
F
de Koning
John
J
Maurice
Madelon M
MM
Hornbeck
Peter
P
Clevers
Hans
H
D000091162:AMP-Activated Protein Kinase Kinases; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D008871:Microvilli / Q000201:enzymology* / Q000648:ultrastructure; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D000099149:Ezrin; D000099317:Hippo Kinases
D000091162:AMP-Activated Protein Kinase Kinases; D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D000099149:Ezrin; C540569:CAB39 protein, human; C476400:STRADA protein, human; C430908:STK26 protein, human; D000099317:Hippo Kinases; C109790:STK11 protein, human