RAB-7 antagonizes LET-23 EGFR signaling during vulva development in Caenorhabditis elegans.

PloS One
Olga Skorobogata, Christian E Rocheleau

Abstract

The Rab7 GTPase regulates late endosome trafficking of the Epidermal Growth Factor Receptor (EGFR) to the lysosome for degradation. However, less is known about how Rab7 activity, functioning late in the endocytic pathway, affects EGFR signaling. Here we used Caenorhabditis elegans vulva cell fate induction, a paradigm for genetic analysis of EGFR/Receptor Tyrosine Kinase (RTK) signaling, to assess the genetic requirements for rab-7. Using a rab-7 deletion mutant, we demonstrate that rab-7 antagonizes LET-23 EGFR signaling to a similar extent, but in a distinct manner, as previously described negative regulators such as sli-1 c-Cbl. Epistasis analysis places rab-7 upstream of or in parallel to lin-3 EGF and let-23 EGFR. However, expression of gfp::rab-7 in the Vulva Presursor Cells (VPCs) is sufficient to rescue the rab-7(-) VPC induction phenotypes indicating that RAB-7 functions in the signal receiving cell. We show that components of the Endosomal Sorting Complex Required for Transport (ESCRT)-0, and -I, complexes, hgrs-1 Hrs, and vps-28, also antagonize signaling, suggesting that LET-23 EGFR likely transits through Multivesicular Bodies (MVBs) en route to the lysosome. Consistent with RAB-7 regulating LET-23 EGFR traffickin...Continue Reading

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Citations

Jan 25, 2013·International Journal of Molecular Sciences·Brian P Ceresa
Feb 8, 2014·PloS One·Joshua J SteffanJames A Cardelli
Feb 14, 2015·Current Opinion in Genetics & Development·Tobias Schmid, Alex Hajnal
Dec 17, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hong-jun WangChuan-lu Jiang
Aug 8, 2015·PloS One·Lin HongLarry A Sklar
Sep 23, 2016·Molecular Biology of the Cell·Olga SkorobogataChristian E Rocheleau
Jul 14, 2017·PloS One·Ryan J GleasonRichard W Padgett
Apr 30, 2017·Journal of Cell Science·Fiona LawChristian E Rocheleau
Dec 14, 2018·Journal of Developmental Biology·Hanna Shin, David J Reiner
Jun 28, 2015·Biologie aujourd'hui·Thomas Juan, Maximilian Fürthauer

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Methods Mentioned

BETA
nucleotide Exchange
GTPases
nucleotide
GTPase
Transgenic

Software Mentioned

Graphpad Prism
AxioVision
LSM Image

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