Unraveling the Mode of Action of a Neuron‐Specific Fluorescent Probe, NeuO: Intracellular Phosphorylation Through PAK6 Kinase
Abstract
Abstract NeuO is an intriguing molecular probe capable of selectively labeling live neurons within a heterogeneous population of brain cells. The precise mechanism responsible for this neuronal labeling has remained a longstanding enigma. We investigated four potential mechanisms underlying NeuO's fluorescence, including its interaction with neuronal proteins, transportation into neurons, export from glial cells, and structural alterations within neurons. Our study found that NeuO undergoes structural changes via phosphorylation by the PAK6 kinase, resulting in high fluorescence in neurons, likely due to fluorogenic activation and intracellular retention within neurons. This discovery improves our understanding of the molecular mechanism of NeuO in neurons and facilitates the development of new chemical compounds that can be selectively modified by kinases in living cells.
Article Details
Authors (12)
Beomsue Kim
Neural Circuits Research Group Korea Brain Research Institute Daegu 41062 Republic of Korea
Dongwan Ko
Neural Circuits Research Group Korea Brain Research Institute Daegu 41062 Republic of Korea
Sang‐Bum Kim
New Drug Development Center Daegu–Gyeongbuk Medical Innovation Foundation (K‐MEDI Hub) Daegu 41061 Republic of Korea
Songhui Kim
Neural Circuits Research Group Korea Brain Research Institute Daegu 41062 Republic of Korea
Minji Kim
Na‐Kyeong Hong
Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
Sun You Park
New Drug Development Center Daegu–Gyeongbuk Medical Innovation Foundation (K‐MEDI Hub) Daegu 41061 Republic of Korea
Wonju Kim
Molecular Neurogenetics Unit, Center for Genomic Medicine, Massachusetts General Hospital
Byoung‐Cheol Lee
Neurovascular Unit Research Group Korea Brain Research Institute Daegu 41062 Republic of Korea
Yunbeom Lee
Taebo Sim
Department of Biomedical Science, Graduate School of Medical Science, Brain Korea 21 Project Yonsei University College of Medicine Seoul 03722 Republic of Korea
Young‐Tae Chang
Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea