Open AccessSaccharomyces cerevisiae Npc2p Is a Functionally Conserved Homologue of the Human Niemann-Pick Disease Type C 2 Protein, hNPC2
Author(s) -
Adam C. Berger,
Thomas H. Vanderford,
Kim M. Gernert,
J. Wylie Nichols,
Víctor Faúndez,
Anita H. Corbett
Publication year - 2005
Publication title -
eukaryotic cell
Language(s) - English
Resource type - Journals
eISSN - 1535-9778
pISSN - 1535-9786
DOI - 10.1128/ec.4.11.1851-1862.2005
Subject(s) - saccharomyces cerevisiae , biology , yeast , npc1 , mutant , biochemistry , secretion , colocalization , mutation , subcellular localization , wild type , cell fractionation , microbiology and biotechnology , gene , transport protein , cell , enzyme , endosome
Niemann-Pick Disease Type C (NP-C) is a fatal neurodegenerative disease, which is biochemically distinguished by the lysosomal accumulation of exogenously derived cholesterol. Mutation of either thehNPC1 orhNPC2 gene is causative for NP-C. We report the identification of the yeast homologue of human NPC2,Saccharomyces cerevisiae Npc2p. We demonstrate that scNpc2p is evolutionarily related to the mammalian NPC2 family of proteins. We also show, through colocalization, subcellular fractionation, and secretion analyses, that yeast Npc2p is treated similarly to human NPC2 when expressed in mammalian cells. Importantly, we show that yeast Npc2p can efficiently revert the unesterified cholesterol and GM1 accumulation seen inhNPC2 −/− patient fibroblasts demonstrating that it is a functional homologue of human NPC2. The present study reveals that the fundamental process of NPC2-mediated lipid transport has been maintained throughout evolution.