RRC ID 45720
Author Delahaye JL, Foster OK, Vine A, Saxton DS, Curtin TP, Somhegyi H, Salesky R, Hermann GJ.
Title Caenorhabditis elegans HOPS and CCZ-1 mediate trafficking to lysosome-related organelles independently of RAB-7 and SAND-1.
Journal Mol Biol Cell
Abstract 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.
Volume 25(7)
Pages 1073-96
Published 2014-4-1
DOI 10.1091/mbc.E13-09-0521
PII mbc.E13-09-0521
PMID 24501423
PMC PMC3967972
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Cytoplasmic Granules / metabolism Embryo, Nonmammalian / cytology Embryo, Nonmammalian / metabolism Endosomes / metabolism Fluorescence Green Fluorescent Proteins / metabolism Intestinal Mucosa / metabolism Intestines / cytology Intestines / embryology Lysosomes / metabolism* Multiprotein Complexes / metabolism* Mutant Proteins / metabolism Protein Transport Suppression, Genetic Vesicular Transport Proteins / metabolism* rab GTP-Binding Proteins / metabolism* rab7 GTP-Binding Proteins
IF 3.791
Times Cited 13
C.elegans tm1125 tm246 tm2253 tm920 tm2504 tm592 tm246 tm1892