Originally published as Genetics Published Articles Ahead of Print on September 9, 2008.

Genetics, Vol. 180, 857-871, October 2008, Copyright © 2008
doi:10.1534/genetics.108.093534

glo-3, a Novel Caenorhabditis elegans Gene, Is Required for Lysosome-Related Organelle Biogenesis

Beverley M. Rabbitts^*,1, Marcela K. Ciotti^,1, Natalie E. Miller, Maxwell Kramer^*, Andrea L. Lawrenson, Steven Levitte, Susan Kremer^*, Elizabeth Kwan^*, Allison M. Weis and Greg J. Hermann^*,,2

^* Program in Biochemistry and Molecular Biology and Department of Biology, Lewis & Clark College, Portland, Oregon 97219

² Corresponding author: Department of Biology, Lewis & Clark College, 0615 S.W. Palatine Hill Rd., Portland, OR 97219.
E-mail: hermann{at}lclark.edu

Gut granules are specialized lysosome-related organelles that act as sites of fat storage in Caenorhabditis elegans intestinal cells. We identified mutations in a gene, glo-3, that functions in the formation of embryonic gut granules. Some glo-3(–) alleles displayed a complete loss of embryonic gut granules, while other glo-3(–) alleles had reduced numbers of gut granules. A subset of glo-3 alleles led to mislocalization of gut granule contents into the intestinal lumen, consistent with a defect in intracellular trafficking. glo-3(–) embryos lacking gut granules developed into adults containing gut granules, indicating that glo-3(+) function may be differentially required during development. We find that glo-3(+) acts in parallel with or downstream of the AP-3 complex and the PGP-2 ABC transporter in gut granule biogenesis. glo-3 encodes a predicted membrane-associated protein that lacks obvious sequence homologs outside of nematodes. glo-3 expression initiates in embryonic intestinal precursors and persists almost exclusively in intestinal cells through adulthood. GLO-3::GFP localizes to the gut granule membrane, suggesting it could play a direct role in the trafficking events at the gut granule. smg-1(–) suppression of glo-3(–) nonsense alleles indicates that the C-terminal half of GLO-3, predicted to be present in the cytoplasm, is not necessary for gut granule formation. Our studies identify GLO-3 as a novel player in the formation of lysosome-related organelles.

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