CPLA₂α targeting to exosomes connects nuclear deformation to LTB₄-signaling during neutrophil chemotaxis.

ABSTRACT: Efficient neutrophil chemotaxis requires the integration of mechanical forces and lipid-mediated signaling. While the signaling lipid leukotriene B4 (LTB₄) reinforces cellular polarity, how mechanical cues regulate its production remains unclear. We now show that cytosolic phospholipase A2α (cPLA₂α), which is essential for the synthesis of LTB₄, functions as a nuclear curvosensor. cPLA₂α responds to nuclear squeezing by localizing to ceramide-rich inner nuclear membrane microdomains and incorporating onto the exofacial surface of nuclear envelope-derived exosomes. This unique topology enables localized LTB₄ synthesis, which synchronizes calcium spikes, promotes myosin light chain II phosphorylation, and sustains polarity and directiona

SUBMITTER: Arya SB 

PROVIDER: S-EPMC12922757 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature