Lats kinase is involved in the intestinal apical membrane integrity in the nematodeCaenorhabditis elegans

Abstract

The roles of Lats kinases in the regulation of cell proliferation and apoptosis have been well established. Here we report new roles for Lats kinase in the integrity of the apical membrane structure. WTS-1, the C. elegans Lats homolog, localized primarily to the subapical region in the intestine. A loss-of-function mutation in wts-1 resulted in an early larval arrest and defects in the structure of the intestinal lumen. An electron microscopy study of terminally arrested wts-1 mutant animals revealed numerous microvilli-containing lumen-like structures within the intestinal cells. The wts-1 phenotype was not caused by cell proliferation or apoptosis defects. Instead, we found that the wts-1 mutant animals exhibited gradual mislocalization of apical actin and apical junction proteins, suggesting that wts-1 normally suppresses the formation of extra apical membrane structures. Heat-shock-driven pulse-chase expression experiments showed that WTS-1 regulates the localization of newly synthesized apical actins. RNAi of the exocyst complex genes suppressed the mislocalization phenotype of wts-1 mutation. Collectively, the data presented here suggest that Lats kinase plays important roles in the integrity of the apical membrane structure of intestinal cells.