PtdIns(3,4)P2, Lamellipodin, and VASP coordinate actin dynamics during phagocytosis in macrophages

• DOI: 10.1083/jcb.202207042
• Publication Date: 2022-09-27T13:36:56Z
• Authors: Fernando Montaño-...; Glenn F.W. Walpole; Matthias Krause; Gerald R.V. Hammond; Sergio Grinstein; Gregory D. Fairn
• Keywords: Pseudopodia

Phosphoinositides are pivotal regulators of vesicular traffic and signaling during phagocytosis. Phagosome formation, the initial step process, is characterized by local membrane remodeling reorganization actin cytoskeleton that leads to formation pseudopods drive particle engulfment. Using genetically encoded fluorescent probes, we found upon engagement a localized pool PtdIns(3,4)P2 generated sequential activities class I phosphoinositide 3-kinases 5-phosphatases. Depletion this locally blocks pseudopod progression ultimately We show effector Lamellipodin (Lpd) recruited nascent phagosomes PtdIns(3,4)P2. Furthermore, silencing Lpd inhibits phagocytosis produces aberrant pseudopodia with disorganized filaments. Finally, vasodilator-stimulated phosphoprotein (VASP) was identified as key actin-regulatory protein mediating phagosome downstream Lpd. Mechanistically, our findings imply pathway involving PtdIns(3,4)P2, Lpd, VASP mediates at stage