The gradient of Gurken, a long-range morphogen, is directly regulated by Cbl-mediated endocytosis

Development
Wei-Ling ChangLi-Mei Pai

Abstract

The asymmetric localization of gurken mRNA and post-translational sorting mechanisms are responsible for the polar distribution of Gurken protein in Drosophila. However, endocytosis of Egfr, the receptor for Gurken in the follicle cells, also plays a role in shaping the extracellular gradient of the Gurken morphogen. Previously, we have found that mutation in the Cbl gene caused elevated Egfr signaling along the dorsoventral axis, and resulted in dorsalization phenotypes in embryos and egg shells. Here, we report that overexpression of the Cbl long isoform significantly changed Gurken distribution. Using an HRP-Gurken fusion protein, we demonstrate that internalization of the Gurken-Egfr complex depends on the activity of Cbl. Increased levels of CblL promote the internalization of this complex, leading to the reduction of free ligands. The Gurken-Egfr complex trafficks through the Rab5/Rab7 associated endocytic pathway to the lysosomal degradation compartment for signaling termination. We observe endocytic Gurken not only in the dorsal but also in the ventral follicle cells, which is, to our knowledge, the first visualization of Gurken on the ventral side of egg chambers. Our results show that Gurken travels towards the latera...Continue Reading

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Citations

Feb 25, 2011·Analytical and Bioanalytical Chemistry·Jen-Cheng WangTzer-En Nee
Oct 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Viktor K LundRobert DeLotto
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Siegfried Roth, Jeremy A Lynch
May 2, 2012·Journal of Biomedical Science·Chiao-Ming LinJui-Chou Hsu
Feb 14, 2012·Journal of Cell Science·Scott B FergusonTrudi Schüpbach
Jul 25, 2014·PLoS Genetics·Mary TruscottMaxim V Frolov
Mar 12, 2009·Experimental Cell Research·Alexander Sorkin, Lai Kuan Goh
Dec 18, 2009·Genesis : the Journal of Genetics and Development·Erika NegreirosHelena Araujo
Aug 25, 2011·Current Opinion in Genetics & Development·Lily S CheungStanislav Y Shvartsman
Nov 13, 2008·Developmental Cell·Nir YakobyStanislav Y Shvartsman
Oct 17, 2017·The EMBO Journal·Patricia Rojas-RíosMartine Simonelig
Jul 31, 2009·Development·Jean-François Boisclair LachanceLaura A Nilson
Jul 12, 2012·Development·David S A SimakovStanislav Y Shvartsman

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