The interaction of ApoA-I and ABCA1 triggers signal transduction pathways to mediate efflux of cellular lipids

Mol Med. 2012 Mar 27;18(1):149-58. doi: 10.2119/molmed.2011.00183.

Abstract

Reverse cholesterol transport (RCT) has been characterized as a crucial step for antiatherosclerosis, which is initiated by ATP-binding cassette A1 (ABCA1) to mediate the efflux of cellular phospholipids and cholesterol to lipid-free apolipoprotein A-I (apoA-I). However, the mechanisms underlying apoA-I/ABCA1 interaction to lead to the lipidation of apoA-I are poorly understood. There are several models proposed for the interaction of apoA-I with ABCA1 as well as the lipidation of apoA-I mediated by ABCA1. ApoA-I increases the levels of ABCA1 protein markedly. In turn, ABCA1 can stabilize apoA-I. The interaction of apoA-I with ABCA1 could activate signaling molecules that modulate posttranslational ABCA1 activity or lipid transport activity. The key signaling molecules in these processes include protein kinase A (PKA), protein kinase C (PKC), Janus kinase 2 (JAK2), Rho GTPases and Ca²⁺, and many factors also could influence the interaction of apoA-I with ABCA1. This review will summarize these mechanisms for the apoA-I interaction with ABCA1 as well as the signal transduction pathways involved in these processes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Apolipoprotein A-I / genetics
  • Apolipoprotein A-I / metabolism*
  • Biological Transport / genetics
  • Biological Transport / physiology
  • Humans
  • Lipid Metabolism / genetics
  • Lipid Metabolism / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoprotein A-I