Article

Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex.

Hubrecht Institute, KNAW and University Medical Centre, Utrecht, The Netherlands.
Developmental cell (impact factor: 13.36). 05/2009; 16(4):551-62. DOI:10.1016/j.devcel.2009.01.016 pp.551-62
Source: PubMed

ABSTRACT 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.

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Keywords

brush border formation
 
brush border induction pathway downstream
 
complex formation
 
data define
 
homologous interaction
 
human Lkb1 kinase
 
Human Mst4 translocates
 
human serine/threonine kinase
 
intestinal epithelial cell
 
invertebrate Par4 polarity gene
 
lateral junctions
 
Lkb1
 
Lkb1 activity
 
Lkb1/Strad/Mo25 polarization complex
 
Mst4 activity inhibits Lkb1-induced brush border formation
 
polarity events
 
regulatory T567 residue
 
subapical membrane compartment
 
yeast Schizosaccharomyces pombe