A novel family of mammalian transmembrane proteins involved in cholesterol transport

Sci Rep. 2017 Aug 7;7(1):7450. doi: 10.1038/s41598-017-07077-z.

Abstract

Cholesterol is an essential compound in mammalian cells because it is involved in a wide range of functions, including as a key component of membranes, precursor of important molecules such as hormones, bile acids and vitamin D. The cholesterol transport across the circulatory system is a well-known process in contrast to the intracellular cholesterol transport, which is poorly understood. Recently in our laboratory, we identified a novel protein in C. elegans involved in dietary cholesterol uptake, which we have named ChUP-1. Insillicoanalysis identified two putative orthologue candidate proteins in mammals. The proteins SIDT1 and SIDT2 share identity and conserved cholesterol binding (CRAC) domains with C. elegans ChUP-1. Both mammalian proteins are annotated as RNA transporters in databases. In the present study, we show evidence indicating that SIDT1 and SIDT2 not only do not transport RNA, but they are involved in cholesterol transport. Furthermore, we show that single point mutations directed to disrupt the CRAC domains of both proteins prevent FRET between SIDT1 and SIDT2 and the cholesterol analogue dehydroergosterol (DHE) and alter cholesterol transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Binding Sites
  • Biological Transport
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / genetics
  • Cell Line
  • Cholesterol / metabolism*
  • Computer Simulation
  • Ergosterol / analogs & derivatives
  • Ergosterol / metabolism
  • HEK293 Cells
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Nucleotide Transport Proteins / chemistry
  • Nucleotide Transport Proteins / genetics*
  • Nucleotide Transport Proteins / metabolism
  • Point Mutation
  • Protein Binding
  • RNA / metabolism

Substances

  • CUP-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Nucleotide Transport Proteins
  • SIDT2 protein, human
  • systemic RNA Interference-defective-1 transmembrane family member 1, human
  • dehydroergosterol
  • RNA
  • Cholesterol
  • Ergosterol