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 microvillicontaining 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 pulsechase 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.

Exocyst Subunits Exo70 and Exo84 Cooperate with Small GTPases to Regulate Behavior and Endocytic Trafficking in C. elegans

“…In yeast, loss-of-function mutations in exocyst subunits block protein secretion and lead to the accumulation of secretory vesicles [6], [7]. In mammalian epithelial cells the exocyst regulates membrane trafficking to the basolateral plasma membrane [8], [9] and regulates the localization of newly synthesized apical actin [10]. In addition, exocyst proteins have been linked to ciliogenesis of the primary cilia in mammalian cells [10], [11].…”

Identification of intestinal ion transport defects in microvillus inclusion disease

“…From the multitude of pathways regulating cellular maturation, we focused on the Hippo pathway since deficiency of the key kinase, WTS-1, leads to the appearance of the MVIs in Caenorhabditis elegans (29). LATS-1, the human homolog of WTS-1, regulates the effector protein YAP1/2 by phosphorylation (62), thus controlling the switch from proliferation to differentiation.…”

Developmental stage-dependent transcriptional regulatory pathways control neuroblast lineage progression

“…Upon activation in Drosophila, Hippo kinase phosphorylates and activates Warts kinase, which inactivates Yorkie by phosphorylation; Yorkie is a transcriptional coactivator of a TEA domain (TEAD) family TF, Scalloped, which induces gene transcription to promote cell proliferation and inhibit apoptosis (Pan, 2010;Zhao et al, 2011). In C. elegans, CST-1/2, WTS-1, YAP-1 and EGL-44 are homologs to Hippo, Warts, Yorkie and Scalloped, respectively, and they play diverse roles in life span, development and neuronal fate determination (Cai et al, 2009;Iwasa et al, 2013;Kang et al, 2009;Wu et al, 2001). However, none of them has been shown to regulate C. elegans cell cycle progression.…”