Intracellular trafficking by Star regulates cleavage of the Drosophila EGF receptor ligand Spitz

Rachel Tsruya, Ayelet Schlesinger, Aderet Reich, Limor Gabay, Amir Sapir, Ben Zion Shilo

Research output: Contribution to journalArticlepeer-review


Spitz (Spi) is a TGFα homolog that is a cardinal ligand for the Drosophila EGF receptor throughout development. Cleavage of the ubiquitously expressed transmembrane form of Spi (mSpi) precedes EGF receptor activation. We show that the Star and Rhomboid (Rho) proteins are necessary for Spi cleavage in Drosophila cells. Complexes between the Spi and Star proteins, as well as between the Star and Rho proteins were identified, but no Spi-Star-Rho triple complex was detected. This observation suggests a sequential activity of Star and Rho in mSpi processing. The interactions between Spi and Star regulate the intracellular trafficking of Spi. The Spi precursor is retained in the periphery of the nucleus. Coexpression of Star promotes translocation of Spi to a compartment where Rho is present both in cells and in embryos. A Star deletion construct that maintains binding to Spi and Rho, but is unable to facilitate Spi translocation, lost biological activity. These results underscore the importance of regulated intracellular trafficking in processing of a TGFα family ligand.

Original languageEnglish
Pages (from-to)222-234
Number of pages13
JournalGenes and Development
Issue number2
StatePublished - 15 Jan 2002
Externally publishedYes


  • EGF receptor
  • Intracellular trafficking
  • Ligand cleavage
  • Rhomboid
  • Spitz
  • Star

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


Dive into the research topics of 'Intracellular trafficking by Star regulates cleavage of the Drosophila EGF receptor ligand Spitz'. Together they form a unique fingerprint.

Cite this