Buchumschlag

Carboxy-terminal fragment of amyloid precursor protein mediates lipid droplet accumulation upon γ-secretase inhibition

γ-Secretase is a protease catalysing the proteolysis of type-I membrane proteins usually after precedent ectodomain shedding of the respective protein substrates. Since proteolysis of membrane proteins is involved in fundamental cellular signaling pathways, dysfunction of γ-secretase can have signif...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Oikawa, Naoto (VerfasserIn) , Fabiano, Marietta (VerfasserIn) , Müller, Ulrike C. (VerfasserIn) , Walter, Jochen (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 17 July 2021
In: Biochemical and biophysical research communications
Year: 2021, Jahrgang: 570, Pages: 137-142
ISSN:1090-2104
DOI:10.1016/j.bbrc.2021.07.021
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbrc.2021.07.021
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006291X21010585
Volltext
Verfasserangaben:Naoto Oikawa, Marietta Fabiano, Ulrike C. Müller, Jochen Walter
Beschreibung
Zusammenfassung:γ-Secretase is a protease catalysing the proteolysis of type-I membrane proteins usually after precedent ectodomain shedding of the respective protein substrates. Since proteolysis of membrane proteins is involved in fundamental cellular signaling pathways, dysfunction of γ-secretase can have significant impact on cellular metabolism and differentiation. Here, we examined the role of γ-secretase in cellular lipid metabolism using neuronally differentiated human SH-SY5Y cells. The pharmacological inhibition of γ-secretase induced lipid droplet (LD) accumulation. The LD accumulation was significantly attenuated by preventing the accumulation of C-terminal fragment of the amyloid precursor protein (APP-CTF), which is a direct substrate of γ-secretase. Additionally, LD accumulation upon γ-secretase inhibition was not induced in APP-knock out (APP-KO) mouse embryonic fibroblasts (MEFs), suggesting significant involvement of APP-CTF accumulation in LD accumulation upon γ-secretase inhibition. On the other hand, γ-secretase inhibition-dependent cholesterol accumulation was not attenuated by inhibition of APP-CTF accumulation in the differentiated SH-SY5Y cells nor in APP-KO MEFs. These results suggest that γ-secretase inhibition can induce accumulation of LD and cholesterol differentially via APP-CTF accumulation.
Beschreibung:Gesehen am 29.09.2021
Beschreibung:Online Resource
ISSN:1090-2104
DOI:10.1016/j.bbrc.2021.07.021

Ähnliche Einträge