619C Poster - 08. Patterning, morphogenesis and organogenesis
Saturday April 09, 1:30 PM - 3:30 PM

Lztr1 is a conserved regulator of Ras/MAPK activity


Authors:
Giovanna Collu; Marek Mlodzik

Affiliation: Icahn School of Medicine at Mount Sinai

Keywords:
z. other (Cell signaling); i. receptor tyrosine kinase/phosphatase

LZTR1 was recently identified in a screen of human chronic myeloid leukaemia cells aimed at discovering the genetic basis of drug resistance mechanisms. Specifically, LZTR1 was shown to regulate RAS ubiquitination and RAS/MAPK pathway activation in cell culture models. Here we demonstrate a conserved function for the fly orthologue Lztr1/CG3711 in regulating Ras activity in vivo. Knockdown of CG3711 leads to Ras gain-of-function phenotypes in the wing, which can be rescued by loss of one copy of Ras. Further, through epistasis experiments we show that CG3711 acts in the Egrf/Ras/MAPK cascade to control wing vein patterning and eye development. Consistently with the involvement of LZTR1 in human disorders affecting the nervous system, such as Schwannomatosis, Drosophila CG3711 is also expressed in specific neurons and glia. We are currently investigating the function of CG3711 in these tissues, and genetic interactions with other homologues involved in similar human pathologies.