title: CUP-1 is a novel protein involved in dietary cholesterol uptake in Caenorhabditis elegans.
abstract: Sterols transport and distribution are essential processes in all multicellular organisms. Survival of the nematode Caenorhabditis elegans depends on dietary absorption of sterols present in the environment. However the general mechanisms associated to sterol uptake in nematodes are poorly understood. In the present work we provide evidence showing that a previously uncharacterized transmembrane protein, designated Cholesterol Uptake Protein-1 (ChUP-1), [corrected] is involved in dietary cholesterol uptake in C. elegans. Animals lacking ChUP-1 [corrected] showed hypersensitivity to cholesterol limitation and were unable to uptake cholesterol. A ChUP-1-GFP [corrected] fusion protein colocalized with cholesterol-rich vesicles, endosomes and lysosomes as well as the plasma membrane. Additionally, by FRET imaging, a direct interaction was found between the cholesterol analog DHE and the transmembrane "cholesterol recognition/interaction amino acid consensus" (CRAC) motif present in C. elegans ChUP-1. [corrected]. In-silico analysis identified two mammalian homologues of ChUP-1. [corrected]. Most interestingly, CRAC motifs are conserved in mammalian ChUP-1 [corrected] homologous. Our results suggest a role of ChUP-1 [corrected] in cholesterol uptake in C. elegans and open up the possibility for the existence of a new class of proteins involved in sterol absorption in mammals.
authors.affiliation: Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, México DF, México.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Valdes
authors.forename: Alejandro
authors.initials: A
authors.lastname: Athie
authors.forename: Laura S
authors.initials: LS
authors.lastname: Salinas
authors.forename: Rosa E
authors.initials: RE
authors.lastname: Navarro
authors.forename: Luis
authors.initials: L
authors.lastname: Vaca
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002791:Cholesterol, Dietary / Q000378:metabolism*; D005298:Fertility / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation
chemical_list: C576227:CUP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002791:Cholesterol, Dietary; D008565:Membrane Proteins