Mammalian ABCG-transporters, sterols and lipids: To bind perchance to transport?

Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Mar;1866(3):158860. doi: 10.1016/j.bbalip.2020.158860. Epub 2020 Dec 11.

Abstract

Members of the ATP binding cassette (ABC) transporter family perform a critical function in maintaining lipid homeostasis in cells as well as the transport of drugs. In this review, we provide an update on the ABCG-transporter subfamily member proteins, which include the homodimers ABCG1, ABCG2 and ABCG4 as well as the heterodimeric complex formed between ABCG5 and ABCG8. This review focusses on progress made in this field of research with respect to their function in health and disease and the recognised transporter substrates. We also provide an update on post-translational regulation, including by transporter substrates, and well as the involvement of microRNA as regulators of transporter expression and activity. In addition, we describe progress made in identifying structural elements that have been recognised as important for transport activity. We furthermore discuss the role of lipids such as cholesterol on the transport function of ABCG2, traditionally thought of as a drug transporter, and provide a model of potential cholesterol binding sites for ABCG2.

Keywords: ABC transporters; Cholesterol; Half-transporters; Lipids.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G / chemistry
  • ATP Binding Cassette Transporter, Subfamily G / genetics
  • ATP Binding Cassette Transporter, Subfamily G / metabolism*
  • Animals
  • Biological Transport, Active
  • Cholesterol / metabolism
  • Humans
  • Lipid Metabolism*
  • Protein Binding
  • Protein Processing, Post-Translational
  • Sterols / metabolism*

Substances

  • ATP Binding Cassette Transporter, Subfamily G
  • Sterols
  • Cholesterol