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CD47 inhibits phagocytosis through Vav dephosphorylation

Wyatt D Miller1, Andrew Manion1, Abhinava K Mishra2

  • 1Interdisciplinary Program in Quantitative Biology, University of California , Santa Barbara, CA, USA.

The Journal of Cell Biology
|October 16, 2025
PubMed

Insights

CD47 protein prevents phagocytosis by inhibiting Rac activation, a key step in engulfing targets. This study reveals Vav as a crucial target in the CD47 signaling pathway, offering new insights into immune regulation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • CD47 is a cell surface protein that inhibits phagocytosis by macrophages.
  • The inhibitory signaling pathway downstream of CD47 receptor SIRPα is not fully understood.
  • Phagocytosis involves complex cytoskeletal rearrangements regulated by small GTPases like Rac and Rho.

Purpose of the Study:

  • To investigate the impact of CD47 on the kinetics of phagocytosis.
  • To elucidate the molecular mechanisms by which CD47 inhibits phagocytosis.
  • To identify key signaling molecules targeted by CD47.

Main Methods:

  • Time-lapse imaging to observe phagocytosis dynamics.
  • Manipulation of Rac and Vav GTPase activity in macrophages.
  • Analysis of protein phosphorylation and recruitment at the phagocytic synapse.

Main Results:

  • CD47 shifted phagocytosis from a Rac-dependent 'reaching' to a Rho-dependent 'sinking' mechanism.
  • Hyperactivation of Rac2 abolished CD47's inhibitory effect.
  • CD47 specifically inhibited Vav phosphorylation, not its recruitment or Syk phosphorylation.
  • Macrophages expressing hyperactive Vav were insensitive to CD47 inhibition.

Conclusions:

  • CD47 inhibits phagocytosis primarily by preventing Rac activation through the suppression of Vav phosphorylation.
  • Vav acts as a critical downstream target of the CD47-SIRPα inhibitory axis.
  • Understanding this pathway provides insights into regulating macrophage-mediated phagocytosis.

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