Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and

Ayako Kataoka1, Yui Koga, Ayumi Uesugi

  • 1Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi, Fukuoka, 812-8582, Japan.

Insights

UDP stimulation activates microglia motility by influencing actin aggregation through vasodilator-stimulated phosphoprotein (VASP) phosphorylation. This pathway involves protein kinase C (PKC) and Rho signaling, crucial for microglial immune functions in the central nervous system.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the primary immune cells of the central nervous system, exhibit dynamic motility essential for their functions like chemotaxis and phagocytosis.
  • Purinergic signaling, particularly through P2Y(6) receptors activated by UDP, is known to modulate microglial motility and phagocytic capacity.
  • The intracellular signaling cascades linking UDP stimulation to actin cytoskeletal rearrangement in microglia remained largely undefined.

Purpose of the Study:

  • To elucidate the intracellular signaling pathway responsible for UDP-induced actin cytoskeletal rearrangement and enhanced motility in microglia.
  • To investigate the role of vasodilator-stimulated phosphoprotein (VASP) phosphorylation in mediating microglial responses to UDP.

Main Methods:

  • Primary rat microglia were stimulated with UDP.
  • Phosphorylation of VASP at Ser157 was assessed.
  • Actin aggregation at the plasma membrane was visualized.
  • The involvement of protein kinase C (PKC) and Rho/G(12/13) signaling pathways was examined using specific inhibitors and genetic manipulation.

Main Results:

  • UDP stimulation rapidly induced transient phosphorylation of VASP at Ser157 in microglia.
  • Phosphorylated VASP accumulated at the plasma membrane, correlating with filamentous (F)-actin aggregation.
  • PKC inhibition suppressed VASP phosphorylation and actin aggregation.
  • Rho inhibition and suppression of G(12/13) signaling also attenuated UDP-induced VASP phosphorylation and actin aggregation.

Conclusions:

  • UDP-induced microglial actin aggregation is mediated by the phosphorylation of VASP.
  • This process is dependent on both protein kinase C (PKC) and Rho/G(12/13) signaling pathways.
  • These findings reveal a key signaling mechanism underlying UDP-driven microglial motility and immune responses.

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