Regulation of Tight Junction Assembly and Epithelial Polarity by a Resident Protein of Apical Endosomes

Abstract

The establishment of tight junctions and cell polarity is an essential process in all epithelia. Endotubin is an integral membrane protein found in apical endosomes of developing epithelia when tight junctions and epithelial polarity first arise. We found that the disruption of endotubin function in cells in culture by siRNA or overexpression of the C-terminal cytoplasmic domain of endotubin causes defects in organization and function of tight junctions. We observe defects in localization of tight junction proteins, reduced transepithelial resistance, increased lanthanum penetration between cells and reduced ability of cells to form cysts in threedimensional culture. In addition, in cells overexpressing the C-terminal domain of endotubin, we observe a delay in re-establishing the normal distribution of endosomes after calcium switch. These results suggest that endotubin regulates trafficking of polarity proteins and tight junction components out of the endosomal compartment, thereby providing a critical link between a resident protein of apical endosomes and tight junctions.

Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1

“…All epithelial cells form adherent junctions provide structural integrity to the epithelium and regulate the actin cytoskeleton. Vertebrate epithelial cells additionally possess tight junctions, which regulate trans-epithelial permeability and distinguish apical and basolateral surfaces [13,14]. Par3, Par6, and aPKC localize to primordial tight junctions and regulate their maturation and position with respect to basolateral and apical membrane domains.…”

Time-resolved Quantitative Proteome Analysis of In Vivo Intestinal Development

“…consistent with the reported presence of endocytic endosomes in rats (Table I). To our knowledge, the expression of apical endosomal glycoprotein along intestinal development has not previously been reported and its function remains to be elucidated (42,43). Our quantification of neonatal Fc receptor and the less characterized apical endosomal glycoprotein shed light onto the postnatal acquisition of passive immunity in mice.…”

Bile acids as metabolic regulators

“…In contrast, Diet1 over-expression increased FGF19 protein secretion by ~3-fold. The function of Diet1 was not clear, but it shares sequence similarity to another protein Endotubin, which might be involved in intracellular protein trafficking (49). Interestingly, Diet1 was shown to interact with FGF19 and co-localize with FGF19 in an intracellular compartment distinct from endosomes/lysosomes in the intestine cell line.…”