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Related Concept Videos

Phosphoinositides and PIPs01:42

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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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Phospholipid localization implies microglial morphology and function via Cdc42 in vitro.

Kyohei Tokizane1, Hiroyuki Konishi1, Kumiko Makide2

  • 1Department of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of Medicine, Nagoya, 65 Tsurumai-cho, Showa-ku, Aichi, 466-8550, Japan.

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Summary

Lysophosphatidylserine (LysoPS) rapidly induces an in vivo-like ramified shape in cultured microglia, independent of receptors. This finding offers a new method for studying microglial function and pathology.

Keywords:
NF-kBlysophospholipidphosphatidylserinepro-inflammatory cytokinesramified microglia

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglia, the immune cells of the central nervous system, display distinct morphologies: ramified when quiescent and amoeboid when activated by injury or inflammation.
  • Manipulating microglial morphology in vitro has been challenging, hindering research into their physiological and pathological roles.

Purpose of the Study:

  • To identify a method for reliably altering microglial morphology in vitro to a ramified, quiescent-like state.
  • To investigate the molecular mechanisms underlying LysoPS-induced morphological changes in microglia.

Main Methods:

  • Primary cultured microglia were treated with lysophosphatidylserine (LysoPS).
  • Morphological changes were assessed, and the involvement of Cdc42 activity and phosphatidylserine (PS) accumulation via the Lands' cycle was investigated.
  • The impact on inflammatory pathways, including NF-kB activity and cytokine production, was evaluated.

Main Results:

  • LysoPS rapidly induced a significant shift in microglial morphology towards an in vivo-like ramified shape, independent of specific receptors.
  • This process was mediated by Cdc42 activation, with LysoPS incorporation into the plasma membrane and conversion to PS.
  • Accumulated PS and Cdc42 localized to microglial processes, and LysoPS treatment suppressed inflammatory cytokine production and NF-kB activity.

Conclusions:

  • Lysophosphatidylserine (LysoPS) provides an effective tool for manipulating microglial morphology in vitro from an amoeboid to a ramified state.
  • This method facilitates studies on microglial physiology and pathology by enabling control over their cellular phenotype.
  • The findings elucidate a receptor-independent mechanism involving Cdc42 and PS accumulation for modulating microglial morphology and inflammatory responses.