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

Authors
Yoonk Sik SungGotina, LizavetaKim, Kyu HyeonLee, Jung YeolSeulgi ShinAziz, HiraKang, Dong MinLiu, XiaoHong, Na-KyeongLee, Hong-GuenLee, Jun-SeokKu, HyeyeongJeong, Cherl hyunPae, Ae NimLim, SungsuChang, Young-TaeKim, Yun Kyung
Issue Date
2024-01
Publisher
John Wiley & Sons Ltd.
Citation
Angewandte Chemie International Edition, v.63, no.3
Abstract
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.
Keywords
CHARMM; GUI; MECHANISMS; DYE; Clathrin-Mediated Endocytosis; Endocytic Trafficking; Fluorescent Probe; Membrane; Neuron
ISSN
1433-7851
URI
https://pubs.kist.re.kr/handle/201004/75732
DOI
10.1002/anie.202312942
Appears in Collections:
KIST Article > 2024
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