Longevity & AgingHow Immune Cells Use a Lipid Signal to Turbocharge Cellular Cleanup
Researchers at St. Jude Children's Research Hospital discovered that receptors triggering LC3-associated phagocytosis (LAP)—a process critical for immune defense and tissue homeostasis—work by clustering the lipid phosphatidylserine (PS) in the phagosome membrane. Using lipidomics, live-cell imaging, and synthetic lipid bilayers, they showed that basic amino acid patches on the intracellular tails of TLR2, CD16, and Tim4 receptors electrostatically attract and cluster PS. This PS enrichment then recruits the Rubicon-PI3-kinase complex, initiating the enzymatic cascade that decorates phagosomes with LC3, accelerating lysosomal digestion. Disrupting PS clustering—by mutating receptor basic patches or sequestering plasma membrane PS—blocked LAP entirely, identifying a unifying lipid-based initiation mechanism across diverse phagocytic receptors.
