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MBC in Press, published online ahead of print August 25, 2004
Mol. Biol. Cell 10.1091/mbc.E04-05-0366

A more recent version of this article appeared on November 1, 2004
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Submitted on May 5, 2004
Revised on August 4, 2004
Accepted on August 10, 2004

A Cycling cis Golgi Protein Mediates Endosome-to-Golgi Traffic

Rajalaxmi Natarajan and Adam D. Linstedt*

Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213

Monitoring Editor: Benjamin Glick

Toxins can invade cells using a direct endosome-to-Golgi endocytic pathway that bypasses late endosomes/prelysosomes. This is also a route used by endogenous proteins including GPP130 which is an integral membrane protein retrieved via the bypass pathway from endosomes to its steady-state location in the cis Golgi. An RNA interference-based test revealed that GPP130 was required for efficient exit of Shiga toxin B-fragment from endosomes en route to the Golgi apparatus. Further, two proteins whose Golgi targeting depends on endosome-to-Golgi retrieval in the bypass pathway accumulated in early/recycling endosomes in the absence of GPP130. GPP130 activity appeared specific to bypass pathway trafficking as the targeting of other tested proteins, including those retrieved to the Golgi via the more conventional late endosome route, was unaltered. Thus, a distally cycling Golgi protein mediates exit from endosomes and thereby underlies Shiga toxin invasion and retrieval-based targeting of other cycling Golgi proteins.

*Corresponding author. E-mail: linstedt{at}andrew.cmu.edu






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