The membrane receptor for plasma retinol-binding protein, a new type of cell-surface receptor

Int Rev Cell Mol Biol. 2011;288:1-41. doi: 10.1016/B978-0-12-386041-5.00001-7.

Abstract

Vitamin A is essential for diverse aspects of life ranging from embryogenesis to the proper functioning of most adult organs. Its derivatives (retinoids) have potent biological activities such as regulating cell growth and differentiation. Plasma retinol-binding protein (RBP) is the specific vitamin A carrier protein in the blood that binds to vitamin A with high affinity and delivers it to target organs. A large amount of evidence has accumulated over the past decades supporting the existence of a cell-surface receptor for RBP that mediates cellular vitamin A uptake. Using an unbiased strategy, this specific cell-surface RBP receptor has been identified as STRA6, a multitransmembrane domain protein with previously unknown function. STRA6 is not homologous to any protein of known function and represents a new type of cell-surface receptor. Consistent with the diverse functions of vitamin A, STRA6 is widely expressed in embryonic development and in adult organ systems. Mutations in human STRA6 are associated with severe pathological phenotypes in many organs such as the eye, brain, heart, and lung. STRA6 binds to RBP with high affinity and mediates vitamin A uptake into cells. This review summarizes the history of the RBP receptor research, its expression in the context of known functions of vitamin A in distinct human organs, structure/function analysis of this new type of membrane receptor, pertinent questions regarding its very existence, and its potential implication in treating human diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Disease
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-2 / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Mutation
  • Phenotype
  • Protein Conformation
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Retinol-Binding Proteins, Plasma / chemistry
  • Retinol-Binding Proteins, Plasma / genetics
  • Retinol-Binding Proteins, Plasma / metabolism*
  • Tissue Distribution
  • Vitamin A / chemistry
  • Vitamin A / metabolism
  • Vitamin A Deficiency / pathology
  • Vitamin A Deficiency / physiopathology

Substances

  • Low Density Lipoprotein Receptor-Related Protein-2
  • Membrane Proteins
  • Receptors, Cell Surface
  • Retinol-Binding Proteins, Plasma
  • STRA6 protein, human
  • retinol binding protein receptor
  • Vitamin A