Akademik Veri Yönetim Sistemi
Tezin Türü: Yüksek Lisans
Tezin Yürütüldüğü Kurum: Acıbadem Mehmet Ali Aydınlar Üniversitesi, Sağlık Bilimleri Enstitüsü, Biyofizik Ana Bilim Dalı, Türkiye
Tezin Onay Tarihi: 2025
Tezin Dili: İngilizce
Öğrenci: GÖKNUR EROL
Danışman: Beki Kan
Özet:
Investigation of Signaling Pathways Activated by the Orphan G Protein-Coupled Receptor GPR37
G Protein-Coupled Receptor 37 (GPR37) has attracted attention due to its role in neuroprotection and its potential as a therapeutic target in neurodegenerative diseases. Prosaposin and its synthetic derivative prosaptide TX14(A) are a potential ligand of GPR37, and its effects on cellular signaling pathways of GPR37 remain under exploration. This study explores the downstream impacts of prosaptide-activated GPR37 on the PI3K-AKT-mTOR signaling pathway. GPR37 activation led to increased phosphorylation of PI3K p85 and mTOR, but a decrease in p70S6K and AKT phosphorylation in GPR37-transfected cells, indicating complex regulation of the pathway. Furthermore, upon prosaptide treatment, GPR37 displayed dynamic changes in its localization, shifting from the plasma membrane to intracellular regions.
The diffusion properties of GPR37 were also investigated using fluorescence correlation spectroscopy (FCS) and giant plasma membrane vesicles (GPMVs). The diffusion coefficient of GPR37 in cells was higher than anticipated for membrane-bound receptors, potentially due to their retention in intracellular compartments. In GPMVs, GPR37 demonstrated lower diffusion coefficients, reflecting the behavior of membrane proteins in a simplified lipid bilayer environment, free from intracellular complexities.
These observations suggest that GPR37 exhibits complex trafficking behavior and diffusion dynamics. While prosaptide activation provides insight into the potential modulation of key cellular pathways, further research is needed to fully uncover the intricate mechanisms underlying GPR37's biological roles.
Keywords: G Protein Coupled Receptor, GPR37, Prosaptide, PI3K-AKT-mTOR, Signaling