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DOCK8 Protein Regulates Macrophage Migration through Cdc42 Protein Activation and LRAP35a Protein Interaction

Akira Shiraishi1,2, Takehito Uruno1,3, Fumiyuki Sanematsu1,3

  • 1From the Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation.

The Journal of Biological Chemistry
|December 29, 2016
PubMed

Insights

Deficiency in DOCK8 protein impairs macrophage migration by disrupting the link between Cdc42 activation and actomyosin dynamics. This highlights DOCK8

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • DOCK8 (dedicator of cytokinesis 8) is an atypical guanine nucleotide exchange factor for Cdc42.
  • Mutations in DOCK8 cause combined immunodeficiency in humans.
  • DOCK8 regulates leukocyte migration and activation, but its mechanism is unclear.

Purpose of the Study:

  • To investigate the role of DOCK8 in macrophage migration.
  • To elucidate the molecular mechanism by which DOCK8 regulates cell motility.

Main Methods:

  • Studied DOCK8-deficient macrophages in 2D migration assays.
  • Performed rescue experiments to assess the requirement of DOCK8's guanine nucleotide exchange factor activity.
  • Investigated the interaction between DOCK8, LRAP35a, and Cdc42 signaling.

Main Results:

  • DOCK8-deficient macrophages exhibit impaired migration.
  • DOCK8's guanine nucleotide exchange factor activity is essential for macrophage migration.
  • DOCK8 associates with LRAP35a to facilitate the phosphorylation of myosin II regulatory light chain, crucial for migration.

Conclusions:

  • DOCK8 is critical for macrophage migration.
  • DOCK8 links Cdc42 activation to actomyosin dynamics via LRAP35a.
  • Disrupting the DOCK8-LRAP35a interaction impairs macrophage motility.
Keywords:
Cdc42actomyosin dynamicscell migrationguanine nucleotide exchange factor (GEF)macrophagesignal transduction

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