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Sorting nexin 5 selectively regulates dorsal-ruffle-mediated macropinocytosis in primary macrophages

Jet Phey Lim1, Prajakta Gosavi1, Justine D Mintern1

  • 1The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010, Australia.

Journal of Cell Science
|October 14, 2015
PubMed

Insights

Sorting nexin 5 (SNX5) selectively regulates macropinocytosis in macrophages by controlling dorsal ruffling and actin polymerization, crucial for immune cell function.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Macropinocytosis is a vital endocytic pathway for immune cell function.
  • The specific pathways governing macropinosome biogenesis remain incompletely understood.
  • Sorting nexin 5 (SNX5) was previously implicated in regulating macropinocytosis.

Purpose of the Study:

  • To investigate the role of SNX5 in macropinocytosis and related cellular processes.
  • To determine if SNX5 regulates distinct macropinocytic pathways.
  • To elucidate the mechanism by which SNX5 influences macropinosome formation.

Main Methods:

  • Utilized SNX5-knockout mice to generate bone-marrow-derived macrophages.
  • Assessed macropinocytic uptake using dextran and ovalbumin.
  • Analyzed phagocytosis, retrograde transport, and antigen presentation.
  • Investigated SNX5 localization and ruffling dynamics upon CSF-1 stimulation.
  • Examined the effect of SNX5 deficiency on actin polymerization.

Main Results:

  • SNX5-deficient macrophages exhibited a 60-70% reduction in macropinocytic uptake.
  • Phagocytosis and retrograde transport were unaffected by SNX5 deficiency.
  • SNX5 localized to actin-rich ruffles upon CSF-1 activation, dependent on receptor tyrosine kinases.
  • SNX5 deficiency significantly impaired dorsal ruffling and macropinosome formation from dorsal ruffles.
  • SNX5 acts upstream of actin polymerization in CSF-1-induced macropinocytosis.

Conclusions:

  • SNX5 plays a critical, selective role in receptor-activated macropinocytosis in macrophages.
  • Dorsal ruffling is a key contributor to macropinosome biogenesis in primary macrophages.
  • SNX5 regulates macropinosomes specifically derived from dorsal ruffles, independent of phagocytosis or dendritic cell function.
Keywords:
Antigen processingDorsal ruffleEndocytosisMacropinocytosisSNX5Sorting nexin

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