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

Wei Ling Chang, Willisa Liou, Hsiao Chung Pen, He Yen Chou, Yu Wei Chang, Wei How Li, Wei Chiang, Li Mei Pai

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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 lateral/ posterior of the egg chamber in the absence of Cbl, suggesting that Cbl actively regulates Gurken distribution through promoting endocytosis and subsequent degradation.

Original languageEnglish
Pages (from-to)1923-1933
Number of pages11
JournalDevelopment
Volume135
Issue number11
DOIs
Publication statusPublished - Jun 2008

Keywords

  • Cbl
  • Drosophila
  • Egfr
  • Endocytosis
  • Gurken
  • Morphogen gradient

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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