Studying the trafficking of labeled trodusquemine and its application as nerve marker for light-sheet and expansion microscopy.
intracellular trafficking
lipid membrane
nerve fiber staining
neurodegeneration
optical imaging
squalamine
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
27
10
2022
received:
06
08
2022
accepted:
01
11
2022
entrez:
24
11
2022
pubmed:
25
11
2022
medline:
26
11
2022
Statut:
ppublish
Résumé
Trodusquemine is an aminosterol with a variety of biological and pharmacological functions, such as acting as an antimicrobial, stimulating body weight loss and interfering with the toxicity of proteins involved in the development of Alzheimer's and Parkinson's diseases. The mechanisms of interaction of aminosterols with cells are, however, still largely uncharacterized. Here, by using fluorescently labeled trodusquemine (TRO-A594 and TRO-ATTO565), we show that trodusquemine binds initially to the plasma membrane of living cells, that the binding affinity is dependent on cholesterol, and that trodusquemine is then internalized and mainly targeted to lysosomes after internalization. We also found that TRO-A594 is able to strongly and selectively bind to myelinated fibers in fixed mouse brain slices, and that it is a marker compatible with tissue clearing and light-sheet fluorescence microscopy or expansion microscopy. In conclusion, this work contributes to further characterize the biology of aminosterols and provides a new tool for nerve labeling suitable for the most advanced microscopy techniques.
Identifiants
pubmed: 36421008
doi: 10.1096/fj.202201276R
pmc: PMC9827910
doi:
Substances chimiques
3-N-1(spermine)-7, 24-dihydroxy-5-cholestane 24-sulfate
0
Cholestanes
0
Spermine
2FZ7Y3VOQX
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22655Informations de copyright
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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