Format

Send to

Choose Destination
J Cell Sci. 2017 Jan 1;130(1):243-259. doi: 10.1242/jcs.188185. Epub 2016 Oct 21.

ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture.

Author information

1
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
2
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
3
Department of Pathology, NorthShore University Health System, Evanston, IL 60201, USA.
4
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
5
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
6
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA.
7
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA jrturner@bwh.harvard.edu.
8
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Abstract

Epithelia within tubular organs form and expand lumens. Failure of these processes can result in serious developmental anomalies. Although tight junction assembly is crucial to epithelial polarization, the contribution of specific tight junction proteins to lumenogenesis is undefined. Here, we show that ZO-1 (also known as TJP1) is necessary for the formation of single lumens. Epithelia lacking this tight junction scaffolding protein form cysts with multiple lumens and are defective in the earliest phases of polarization, both in two and three dimensions. Expression of ZO-1 domain-deletion mutants demonstrated that the actin-binding region and U5-GuK domain are crucial to single lumen development. For actin-binding region, but not U5-GuK domain, mutants, this could be overcome by strong polarization cues from the extracellular matrix. Analysis of the U5-GuK binding partners shroom2, α-catenin and occludin showed that only occludin deletion led to multi-lumen cysts. Like ZO-1-deficiency, occludin deletion led to mitotic spindle orientation defects. Single lumen formation required the occludin OCEL domain, which binds to ZO-1. We conclude that ZO-1-occludin interactions regulate multiple phases of epithelial polarization by providing cell-intrinsic signals that are required for single lumen formation.

KEYWORDS:

Cell polarity; Epithelial Cells; Lumen Formation; Morphogenesis; Tight junctions

PMID:
27802160
PMCID:
PMC5394778
DOI:
10.1242/jcs.188185
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center