The ortholog of the human proto‐oncogene ROS1 is required for epithelial development in C. elegans

Abstract

The orphan receptor ROS1 is a human proto-oncogene, mutations of which are found in an increasing number of cancers. Little is known about the role of ROS1, however in vertebrates it has been implicated in promoting differentiation programs in specialized epithelial tissues. In this study we show that the C. elegans ortholog of ROS1, the receptor tyrosine kinase ROL-3, has an essential role in orchestrating the morphogenesis and development of specialized epidermal tissues, highlighting a potentially conserved function in coordinating crosstalk between developing epithelial cells. We also provide evidence of a direct relationship between ROL-3, the mucin SRAP-1, and BCC-1, the homolog of mRNA regulating protein Bicaudal-C. This study answers a longstanding question as to the developmental function of ROL-3, identifies three new genes that are expressed and function in the developing epithelium of C. elegans, and introduces the nematode as a potentially powerful model system for investigating the increasingly important, yet poorly understood, human oncogene ROS1. genesis 51:545–561.

The conserved, secreted protease inhibitor MLT-11 is necessary for C. elegans molting and embryogenesis

“…How does a protease inhibitor mutation cause a roller phenotype? Aside from mlt-11 , the only non-collagen roller gene is rol-3 , which encodes a predicted receptor tyrosine kinase (Jones et al, 2013). ROL-3 is hypodermally expressed and necessary for ecdysis and cuticle formation (Jones et al, 2013).…”

“…Aside from mlt-11 , the only non-collagen roller gene is rol-3 , which encodes a predicted receptor tyrosine kinase (Jones et al, 2013). ROL-3 is hypodermally expressed and necessary for ecdysis and cuticle formation (Jones et al, 2013). rol-3 mutations cause defects in seam cell formation and mlt-11 is necessary in seam cells for developmental progression and molting (Fig.…”

Polymorphism of Rs9387478 Correlates with Overall Survival in Female Nonsmoking Patients with Lung Cancer

“…The orphan receptor ROS1 is a human proto-oncogene, mutations of which are found in an increasing number of cancers (10). ROS1 encodes a tyrosine kinase that is abnormally expressed and translocated in both brain and lung cancers (11).…”

Pathways that affect anterior morphogenesis inC. elegansembryos

“…Consistent with a role for MLT-7 in the aECM, a fosmid-based MLT-7::GFP reporter localized to the larval cuticle (Fig 5B). Other candidate aECM regulators included the receptor tyrosine kinase ROL-3 (Jones et al, 2013); the neprilysin-family peptidase NEP-1 (Spanier et al, 2005), an ortholog of the human endoplasmic reticulum peptidase F49B2.6/ERAP1; and a Patched-related protein, PTR-23, implicated in molting and membrane integrity (Choi et al, 2016;Zugasti et al, 2005). In addition, the screen identified several uncharacterized proteins as well as proteins with conserved motifs but with no previous connection to aECM biology.…”