Caenorhabditis elegans

SAND-1

CELE_F41H10.11, F41H10.11
sand-1 encodes an ortholog of human MON1A and MON1B and S. cerevisiae MON1, required for normal association of RAB-7 with the membrane, and thus also required for normal (RAB-7-mediated) traffic between early and late endosomes; SAND-1 has a SAND/DUF254 domain, which has structural similarity to longins and distant similarity to human HPS1 (OMIM:604982); SAND-1, like its yeast ortholog Mon1p, binds the CHiPS domain protein F58G11.6 (CCZ-1/HPS-4); sand-1(or552) mutants phenotypically resemble rab-7(ok511) or rab-7(RNAi) animals, with strongly defective endocytosis but normal lysosomes; unlike RAB-7, SAND-1 is cytoplasmic, and its localization is unaffected by loss of RAB-7 function; sand-1(or552) mutants can begin uptake of yolk protein or soluble GFP by oocytes or coelomocytes normally, but further intracellular transport (to oocyte yolk granules or coelomocyte lysosomes) being delayed or blocked; sand-1(or552) mutants accumulate excess RAB-5 and RAB-7, though rab-5(RNAi) animals do not resemble sand-1(or552) or rab-7(RNAi) ones; by orthology with Mon1p, SAND-1 may also be required for autophagy; SAND-1 acts cell-autonomously, and is necessary for embryonic viability and development, with an absolute zygotic requirement and a partial maternal one; sand-1(or552) or sand-1(RNAi) escapers have abnormal body shapes and movement; transgenic SAND-1 partially rescues a mon1 deletion in yeast.
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