Drosophila EGFR signalling is modulated by differential compartmentalization of Rhomboid intramembrane proteases

Shaul Yogev, Eyal D Schejter, Ben‐Zion Shilo

Author Affiliations

  1. Shaul Yogev1,
  2. Eyal D Schejter1 and
  3. Ben‐Zion Shilo*,1
  1. 1 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
  1. *Corresponding author. Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. Tel: +972 8 9343169; Fax: +972 8 9344108; E‐mail: benny.shilo{at}
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We explore the role of differential compartmentalization of Rhomboid (Rho) proteases that process the Drosophila EGF receptor ligands, in modulating the amount of secreted ligand and consequently the level of EGF receptor (EGFR) activation. The mSpitz ligand precursor is retained in the ER, and is trafficked by the chaperone Star to a late compartment of the secretory pathway, where Rho‐1 resides. This work demonstrates that two other Rho proteins, Rho‐2 and Rho‐3, which are expressed in the germ line and in the developing eye, respectively, cleave the Spitz precursor and Star already in the ER, in addition to their activity in the late compartment. This property attenuates EGFR activation, primarily by compromising the amount of chaperone that can productively traffic the ligand precursor to the late compartment, where cleavage and subsequent secretion take place. These observations identify changes in intracellular compartment localization of Rho proteins as a basis for signal attenuation, in tissues where EGFR activation must be highly restricted in space and time.

  • Received October 23, 2007.
  • Accepted February 29, 2008.
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