Drosophila NPC1b Promotes an Early Step in Sterol Absorption from the Midgut Epithelium

Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Cell Metabolism (Impact Factor: 17.57). 04/2007; 5(3):195-205. DOI: 10.1016/j.cmet.2007.01.011
Source: PubMed

ABSTRACT The NPC1 family of proteins plays crucial roles in the intestinal absorption and intracellular trafficking of sterols. The Drosophila genome encodes two NPC1 homologs, one of which, NPC1a, is required for intracellular sterol trafficking in many tissues. Here we show that the other Drosophila NPC1 family member, NPC1b, is expressed in the midgut epithelium and that NPC1b is essential for growth during the early larval stages of development. NPC1b mutants are severely defective in sterol absorption, and the midgut epithelium of NPC1b mutants is deficient in sterols and sterol trafficking intermediates. By contrast, NPC1a mutants absorb sterols more efficiently than wild-type animals, and, unexpectedly, NPC1b;NPC1a double mutants absorb sterols as efficiently as wild-type animals. Together, these findings suggest that NPC1b plays an early role in sterol absorption, although sterol absorption continues at high efficiency through an NPC1a- and NPC1b-independent mechanism under conditions of impaired intracellular sterol trafficking.

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    • "t al . , 2010 ) . Tissue - specific transcript abundance analysis revealed that in uninfected mosquitoes , AaegML33 was constitutively expressed in the midgut and fat body - containing carcass ( Fig . 6 ) . In contrast , AaegNPC1b expression was limited mainly to the mosquito mid - gut , which corresponds to the expression of NPC1b in Drosophila ( Voght et al . , 2007 ) , suggesting that the biological role of the NPC1b gene may be conserved among insects . The increase in the transcript abundance of the AaegNPC1b and AaegML33 genes after the ingestion of DENV - infected blood meal ( Fig . 7 ) suggests that DENV may up - regulate the expression of both genes to pre - vent immune activation or suppres"
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