NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neurons.

Autor: Sung Y; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Gotina L; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea., Kim KH; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea., Lee JY; Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea., Shin S; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Aziz H; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea., Kang DM; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.; Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea., Liu X; Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea., Hong NK; Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea., Lee HG; Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea., Lee JS; Department of Pharmacology, Korea University College of Medicine, Seoul, 02841, Republic of Korea., Ku H; Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, 02447, Republic of Korea., Jeong C; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea.; Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Pae AN; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea., Lim S; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Chang YT; Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea., Kim YK; Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Jan 15; Vol. 63 (3), pp. e202312942. Date of Electronic Publication: 2023 Dec 15.
DOI: 10.1002/anie.202312942
Abstrakt: The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined. Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons. In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001). Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin-mediated endocytosis. Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61). Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers. The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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