Intracellular trafficking by Star regulates cleavage of the Drosophila EGF receptor ligand Spitz.
Spitz (Spi) is a TGFalpha 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 TGFalpha family ligand.
Tsruya
Rachel
R
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Schlesinger
Ayelet
A
Reich
Aderet
A
Gabay
Limor
L
Sapir
Amir
A
Shilo
Ben-Zion
BZ
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors / Q000378:metabolism*; D006868:Hydrolysis; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; C081481:Rho protein, Drosophila; C415248:S protein, Drosophila; C472498:Stet protein, Drosophila; C076026:spi protein, Drosophila; D004815:Epidermal Growth Factor; D066246:ErbB Receptors