RRC ID |
59388
|
Author |
Morris C, Foster OK, Handa S, Peloza K, Voss L, Somhegyi H, Jian Y, Vo MV, Harp M, Rambo FM, Yang C, Hermann GJ.
|
Title |
Function and regulation of the Caenorhabditis elegans Rab32 family member GLO-1 in lysosome-related organelle biogenesis.
|
Journal |
PLoS Genet
|
Abstract |
Cell type-specific modifications of conventional endosomal trafficking pathways lead to the formation of lysosome-related organelles (LROs). C. elegans gut granules are intestinally restricted LROs that coexist with conventional degradative lysosomes. The formation of gut granules requires the Rab32 family member GLO-1. We show that the loss of glo-1 leads to the mistrafficking of gut granule proteins but does not significantly alter conventional endolysosome biogenesis. GLO-3 directly binds to CCZ-1 and they both function to promote the gut granule association of GLO-1, strongly suggesting that together, GLO-3 and CCZ-1 activate GLO-1. We found that a point mutation in GLO-1 predicted to spontaneously activate, and function independently of it guanine nucleotide exchange factor (GEF), localizes to gut granules and partially restores gut granule protein localization in ccz-1(-) and glo-3(-) mutants. CCZ-1 forms a heterodimeric complex with SAND-1(MON1), which does not function in gut granule formation, to activate RAB-7 in trafficking pathways to conventional lysosomes. Therefore, our data suggest a model whereby the function of a Rab GEF can be altered by subunit exchange. glo-3(-) mutants, which retain low levels of GLO-3 activity, generate gut granules that lack GLO-1 and improperly accumulate RAB-7 in a SAND-1 dependent process. We show that GLO-1 and GLO-3 restrict the distribution of RAB-7 to conventional endolysosomes, providing insights into the segregation of pathways leading to conventional lysosomes and LROs.
|
Volume |
14(11)
|
Pages |
e1007772
|
Published |
2018-11-1
|
DOI |
10.1371/journal.pgen.1007772
|
PII |
PGENETICS-D-18-00362
|
PMID |
30419011
|
PMC |
PMC6268011
|
MeSH |
Animals
Animals, Genetically Modified
Caenorhabditis elegans / embryology
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / chemistry
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Cytoplasmic Granules / metabolism
Digestive System / embryology
Digestive System / metabolism
Genes, Helminth
Lysosomes / metabolism
Mutation
Organelle Biogenesis
Protein Interaction Domains and Motifs
Vesicular Transport Proteins / chemistry
Vesicular Transport Proteins / genetics
Vesicular Transport Proteins / metabolism
rab GTP-Binding Proteins / chemistry
rab GTP-Binding Proteins / genetics
rab GTP-Binding Proteins / metabolism*
|
IF |
5.224
|
Times Cited |
4
|
Resource |
C.elegans |
tm920
tm1892
tm1125
tm592
tm2241 |