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MBC in Press, published online ahead of print January 3, 2007
Mol. Biol. Cell 10.1091/mbc.E06-08-0685

A more recent version of this article appeared on March 1, 2007
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Submitted on August 7, 2006
Revised on December 19, 2006
Accepted on December 22, 2006

Function of the Caenorhabditis elegans ABC Transporter PGP-2 in the Biogenesis of a Lysosome-related Fat Storage Organelle

Lena K. Schroeder,* Susan Kremer,{dagger}{ddagger} Maxwell J. Kramer,{dagger}{ddagger} Erin Currie,*{dagger} Elizabeth Kwan,{dagger} Jennifer L. Watts,{sect} Andrea L. Lawrenson,* and Greg J. Hermann*{dagger}

*Department of Biology and {dagger}Program in Biochemistry and Molecular Biology, Lewis & Clark College, Portland, OR 97219; {sect}Institute of Biological Chemistry, Washington State University, Pullman, WA 99164

Monitoring Editor: Sandra Lemmon

Caenorhabditis elegans gut granules are intestine specific lysosome-related organelles with birefringent and autofluorescent contents. We identified pgp-2, which encodes an ABC transporter, in screens for genes required for the proper formation of gut granules. pgp-2(-) embryos mislocalize birefringent material into the intestinal lumen and are lacking in acidified intestinal V-ATPase containing compartments. Adults without pgp-2(+) function similarly lack organelles with gut granule characteristics. These cellular phenotypes indicate that pgp-2(-) animals are defective in gut granule biogenesis. Double mutant analysis suggests that pgp-2(+) functions in parallel with the AP-3 adaptor complex during gut granule formation. We find that pgp-2 is expressed in the intestine where it functions in gut granule biogenesis and that PGP-2 localizes to the gut granule membrane. These results support a direct role of an ABC transporter in regulating lysosome biogenesis. Previously, pgp-2(+) activity has been shown to be necessary for the accumulation of Nile Red stained fat in C. elegans. We show that gut granules are sites of fat storage in C. elegans embryos and adults. Notably, levels of triacylglycerides are relatively normal in animals defective in the formation of gut granules. Our results provide an explanation for the loss of Nile Red stained fat in pgp-2(-) animals as well as insight into the specialized function of this lysosome-related organelle.

{ddagger}These authors contributed equally to this work.

Address correspondence to: Greg J. Hermann (hermann{at}lclark.edu)




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