Caenorhabditis elegans LET-413 Scribble is essential in the epidermis for growth, viability, and directional outgrowth of epithelial seam cells.

Amalia Riga,Janine Cravo,Helena R Pires,Victoria G Castiglioni,Sander Van Den Heuvel,Ruben Schmidt,Mike Boxem,Jeremy Nance

doi:10.1371/journal.pgen.1009856

Abstract

The conserved adapter protein Scribble (Scrib) plays essential roles in a variety of cellular processes, including polarity establishment, proliferation, and directed cell migration. While the mechanisms through which Scrib promotes epithelial polarity are beginning to be unraveled, its roles in other cellular processes including cell migration remain enigmatic. In C. elegans, the Scrib ortholog LET-413 is essential for apical-basal polarization and junction formation in embryonic epithelia. However, whether LET-413 is required for postembryonic development or plays a role in migratory events is not known. Here, we use inducible protein degradation to investigate the functioning of LET-413 in larval epithelia. We find that LET-413 is essential in the epidermal epithelium for growth, viability, and junction maintenance. In addition, we identify a novel role for LET-413 in the polarized outgrowth of the epidermal seam cells. These stem cell-like epithelial cells extend anterior and posterior directed apical protrusions in each larval stage to reconnect to their neighbors. We show that the role of LET-413 in seam cell outgrowth is likely mediated largely by the junctional component DLG-1 discs large, which we demonstrate is also essential for directed outgrowth of the seam cells. Our data uncover multiple essential functions for LET-413 in larval development and show that the polarized outgrowth of the epithelial seam cells is controlled by LET-413 Scribble and DLG-1 Discs large.

Highlights

Epithelial cells establish molecularly and functionally distinct apical, basal, and lateral membrane domains to function as selectively permeable barriers
In this paper we study the role of Scribble during larval development of the small nematode Caenorhabditis elegans
Because LET-413 depletion resulted in disruptions in the integrity of cell junctions, we investigated the roles of the DLG-1/AJM-1 and cadherin-catenin junctional complexes in protrusion formation

Summary

Introduction

Epithelial cells establish molecularly and functionally distinct apical, basal, and lateral membrane domains to function as selectively permeable barriers. Epithelial cell polarity is established through mutually antagonistic interactions between conserved groups of cortical polarity regulators, including the Par, Crumbs and Scribble modules [1,2,3,4]. The Scribble polarity module, which consists of the proteins Scribble (Scrib), discs large (Dlg), and lethal giant larvae (Lgl), plays conserved roles in the establishment of basolateral identity and formation of cell junctions [5,6,7,8,9,10,11,12,13]. Scribble module proteins are involved in the regulation of cell proliferation and migration. In Drosophila, scrib, dlg, and lgl function as suppressors of neoplastic overgrowth of imaginal disks [14,15,16,17]. Many human tumors show altered Scrib protein levels or protein mislocalization, and in both Drosophila and mammalian tumor models, loss of Scrib increases the malignant and metastatic potential of oncogenic stimuli such as activation of Ras, Raf, Notch or Akt [18,19,20,21]

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