Caenorhabditis elegans

NCR-1

CELE_F02E8.6, npc-1, F02E8.6
ncr-1 encodes a large transmembrane glycoprotein with a patched-like domain that is orthologous to human NPC1; NCR-1 and NPC1 are eukaryotic members of the resistance-nodulation-division (RND) family of membrane permeases, and have a putative sterol-sensing domain; by homology, NCR-1 is predicted to function in intracellular cholesterol and glycolipid trafficking; in C. elegans, NCR-1 is required for growth and survival in the absence of cholesterol, newly hatched ncr-1 mutant larvae grow poorly on cholesterol-free medium and die at the L1 or L2 stage; NCR-1 is also involved in negative regulation of dauer formation, being required redundantly with NCR-2, a second C. elegans NPC1-like protein, for preventing constitutive dauer formation; dauer formation in ncr-1; ncr-2 double mutants is suppressed by mutations in daf-12, which encodes a steroid hormone receptor, and by overexpression of daf-9, which encodes a cytochrome P450, suggesting that NCR-1 and NCR-2 may function to transport a sterol precursor that is metabolized by DAF-9 to then serve as the DAF-12 ligand.
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