glo-3, a novel Caenorhabditis elegans gene, is required for lysosome-related organelle biogenesis

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

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)857-871
Number of pages15
JournalGenetics
Volume180
Issue number2
DOIs
StatePublished - Oct 2008
Externally publishedYes

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