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Cell migration is negatively modulated by ABCA1.

Shiho Ito1, Noriyuki Kioka1,2, Kazumitsu Ueda1,2

  • 1a Division of Applied Life Sciences, Graduate School of Agriculture , Kyoto University , Kyoto , Japan.

Bioscience, Biotechnology, and Biochemistry
|November 18, 2018
PubMed
Summary
This summary is machine-generated.

ATP-Binding Cassette A1 (ABCA1) protein regulates cell migration by influencing plasma membrane lipid distribution and Rac1/MEK-ERK signaling pathways. ABCA1 knockdown accelerates cell migration, while inhibiting these pathways suppresses it.

Keywords:
ABCA1ERKcell densitycell migrationcholesterol

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Plasma membrane lipid distribution is crucial for cellular functions.
  • ATP-Binding Cassette A1 (ABCA1) is a key lipid transporter involved in high-density lipoprotein generation.
  • ABCA1 has been shown to maintain asymmetric cholesterol distribution in the plasma membrane.

Purpose of the Study:

  • To investigate the role of ABCA1 in cell migration.
  • To elucidate the signaling pathways modulated by ABCA1 in relation to cell migration.
  • To determine if ABCA1 affects cell migration independently of cellular cholesterol content.

Main Methods:

  • ABCA1 knockdown in mouse embryonic fibroblasts.
  • Assessment of cell migration rates.
  • Analysis of Rac1 activation and localization to detergent-resistant membranes.
  • Measurement of MEK and ERK phosphorylation.
  • Inhibition of Rac1 and MEK-ERK signaling pathways.

Main Results:

  • ABCA1 knockdown accelerated cell migration.
  • ABCA1 knockdown increased Rac1 activation and its localization to detergent-resistant membranes.
  • Phosphorylation of MEK and ERK was increased in ABCA1 knockdown cells.
  • Inhibition of Rac1 or MEK-ERK signaling suppressed cell migration in ABCA1 knockdown cells.
  • Cellular cholesterol content remained unchanged under experimental conditions.

Conclusions:

  • ABCA1 suppresses cell migration by modulating Rac1 and MEK-ERK signaling pathways.
  • The effect of ABCA1 on cell migration is linked to alterations in plasma membrane lipid distribution, not overall cellular cholesterol levels.
  • ABCA1 plays a significant role in regulating cell motility through specific intracellular signaling cascades.