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

被引：102

作者：

Tsruya, R ^{[1
]}

Schlesinger, A ^{[1
]}

Reich, A ^{[1
]}

Gabay, L ^{[1
]}

Sapir, A ^{[1
]}

Shilo, BZ ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel

来源：

GENES & DEVELOPMENT | 2002年 / 16卷 / 02期

关键词：

Spitz; Star; Rhomboid; EGF receptor; intracellular trafficking; ligand cleavage;

D O I：

10.1101/gad.214202

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 TGFa family ligand.

引用

页码：222 / 234

页数：13

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