Caenorhabditis elegansHOPS and CCZ-1 mediate trafficking to lysosome-related organelles independently of RAB-7 and SAND-1
| Autor: | Greg J. Hermann, Hannah Somhegyi, Thomas P. Curtin, Daniel S. Saxton, Annalise Vine, Rebecca Salesky, Olivia K. Foster, Jared L. Delahaye |
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| Rok vydání: | 2014 |
| Předmět: |
Embryo
Nonmammalian Endosome Green Fluorescent Proteins Vesicular Transport Proteins Endosomes Cytoplasmic Granules Fluorescence Suppression Genetic Gut granule Lysosome medicine Animals Intestinal Mucosa Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology biology rab7 GTP-Binding Proteins Articles Cell Biology biology.organism_classification Transport protein Cell biology Intestines Protein Transport medicine.anatomical_structure Biochemistry Membrane Trafficking rab GTP-Binding Proteins Multiprotein Complexes Mutant Proteins Rab Guanine nucleotide exchange factor Lysosomes Biogenesis |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e13-09-0521 |
| Popis: | This work presents a systematic analysis of how VPS-C/HOPS, CCZ-1/SAND-1, and RAB-7, which have well-defined roles in lysosome formation, act in the biogenesis of Caenorhabditis elegans lysosome-related organelles. It identifies key molecular similarities and differences in trafficking to these homologous, yet distinct organelles. As early endosomes mature, the SAND-1/CCZ-1 complex acts as a guanine nucleotide exchange factor (GEF) for RAB-7 to promote the activity of its effector, HOPS, which facilitates late endosome–lysosome fusion and the consumption of AP-3–containing vesicles. We show that CCZ-1 and the HOPS complex are essential for the biogenesis of gut granules, cell type–specific, lysosome-related organelles (LROs) that coexist with conventional lysosomes in Caenorhabditis elegans intestinal cells. The HOPS subunit VPS-18 promotes the trafficking of gut granule proteins away from lysosomes and functions downstream of or in parallel to the AP-3 adaptor. CCZ-1 also acts independently of AP-3, and ccz-1 mutants mistraffic gut granule proteins. Our results indicate that SAND-1 does not participate in the formation of gut granules. In the absence of RAB-7 activity, gut granules are generated; however, their size and protein composition are subtly altered. These observations suggest that CCZ-1 acts in partnership with a protein other than SAND-1 as a GEF for an alternate Rab to promote gut granule biogenesis. Point mutations in GLO-1, a Rab32/38-related protein, predicted to increase spontaneous guanine nucleotide exchange, specifically suppress the loss of gut granules by ccz-1 and glo-3 mutants. GLO-3 is known to be required for gut granule formation and has homology to SAND-1/Mon1–related proteins, suggesting that CCZ-1 functions with GLO-3 upstream of the GLO-1 Rab, possibly as a GLO-1 GEF. These results support LRO formation occurring via processes similar to conventional lysosome biogenesis, albeit with key molecular differences. |
| Databáze: | OpenAIRE |
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