Lysosomal PIP 3 revealed by genetically encoded lipid biosensors

• DOI: 10.1073/pnas.2426929122
• Publication Date: 2025-03-24T19:13:45Z
• Authors: Ayse Z. Sahan; Mingyuan Chen; Qi Su; Qingrong Li; Dong Wang; Jin Zhang
• Keywords: Internalization; Second messenger system

3-Phosphoinositides (3-PIs), phosphatidylinositol (3,4) bisphosphate [PI(3,4)P 2 ] and (3,4,5) trisphosphate (PIP 3 ), are important lipid second messengers in the Phosphoinositide 3-Kinase (PI3K)/Akt signaling pathway, which is crucial to cell growth frequently dysregulated cancer. Emerging evidence suggests these may be present membranes beyond plasma membrane, yet their spatial regulation within other membrane compartments not well understood. To dissect of specific 3-PI species, we developed genetically encodable biosensors with selectivity for PIP or PI(3,4)P . Using biosensors, showed that significantly accumulated at lysosome upon factor stimulation, contrast conventional view exclusively membrane. Furthermore, lysosomal originates from relies on dynamin-dependent endocytosis internalization. Thus, can exploit dynamic trafficking pathways access subcellular regulate a spatially selective manner.