Cell migration is negatively modulated by ABCA1

Biosci Biotechnol Biochem. 2019 Mar;83(3):463-471. doi: 10.1080/09168451.2018.1547105. Epub 2018 Nov 16.

Abstract

Temporal and spatial changes of membrane lipid distribution in the plasma membrane are thought to be important for various cellular functions. ATP-Binding Cassette A1 (ABCA1) is a key lipid transporter for the generation of high density lipoprotein. Recently, we reported that ABCA1 maintains an asymmetric distribution of cholesterol in the plasma membrane. Here we report that ABCA1 suppresses cell migration by modulating signal pathways. ABCA1 knockdown in mouse embryonic fibroblasts accelerated cell migration and increased activation of Rac1 and its localization to detergent-resistant membranes. Phosphorylation of MEK and ERK also increased. Inhibition of Rac1 or MEK-ERK signals suppressed cell migration in ABCA1 knockdown cells. Because our experimental conditions for cell migration did not contain cholesterol or lipid acceptors for ABCA1, cellular cholesterol content was not changed. These data suggest that ABCA1 modulates cell migration via Rac1 and MEK-ERK signaling by altering lipid distribution in the plasma membrane.

Keywords: ABCA1; ERK; cell density; cell migration; cholesterol.

MeSH terms

  • ATP Binding Cassette Transporter 1 / deficiency
  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism*
  • Animals
  • Cell Count
  • Cell Membrane / metabolism
  • Cell Movement*
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Mice
  • Protein Transport
  • rac1 GTP-Binding Protein / metabolism

Substances

  • ATP Binding Cassette Transporter 1
  • Extracellular Signal-Regulated MAP Kinases
  • rac1 GTP-Binding Protein