A cell-permeable fluorescent probe reveals temporally diverse PI(4,5)P2 dynamics evoked by distinct GPCR agonists in neurons.
Chemical science June 18, 2025 Rajasree Kundu, Samsuzzoha Mondal, Akshay Kapadia et al. 4 citations
A new fluorescent sensor rapidly enters living cells, neurons, and whole organisms to track the lipid PI(4,5)P2 in real time. Using this probe, the authors show that a hallucinogenic ligand at the serotonin2A receptor depletes PI(4,5)P2 more slowly during the first seconds after binding than a non-hallucinogenic ligand, but its effect lasts longer. This difference in early lipid dynamics may underlie the contrasting behavioral effects of hallucinogenic versus non-hallucinogenic drugs. The sensor offers a tool for observing early molecular events in neuronal signaling.