GPR155

Last update 08 May 2025

Basic Info

Synonyms

DEP.7, DEPDC3, FLJ31819

+ [5]

Introduction

Cholesterol-binding protein that acts as a regulator of mTORC1 signaling pathway (PubMed:36007018). Acts as a sensor of cholesterol to signal cholesterol sufficiency to mTORC1: in presence of cholesterol, binds cholesterol, leading to disrupt interaction between the GATOR1 and KICSTOR complexes and promote mTORC1 signaling (PubMed:36007018). Upon cholesterol starvation, GPR155/LYCHOS is unable to perturb the association between GATOR1 and KICSTOR, leading to mTORC1 signaling inhibition (PubMed:36007018).

100 Clinical Results associated with GPR155

100 Translational Medicine associated with GPR155

0 Patents (Medical) associated with GPR155

Literatures (Medical) associated with GPR155

01 May 2024·Immunity

25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages

Article

Author: Chen, Longlong ; Li, Weiyun ; Shen, Huan ; Su, Chen ; Wu, Sifan ; Yang, Dan ; Wang, Shuang ; Dong, Chen ; Hui, Lijian ; Wang, Mingchang ; Wei, Bin ; Han, Mingshun ; Wang, Hongyan ; Hu, Miao ; Zheng, Yuxiao ; Xiao, Jun ; Dang, Yuanhao ; Ding, Xinyu ; Li, Na ; Ye, Youqiong ; Tang, Huiru

Macrophages are critical to turn noninflamed "cold tumors" into inflamed "hot tumors". Emerging evidence indicates abnormal cholesterol metabolites in the tumor microenvironment (TME) with unclear function. Here, we uncovered the inducible expression of cholesterol-25-hydroxylase (Ch25h) by interleukin-4 (IL-4) and interleukin-13 (IL-13) via the transcription factor STAT6, causing 25-hydroxycholesterol (25HC) accumulation. scRNA-seq analysis confirmed that CH25H^hi subsets were enriched in immunosuppressive macrophage subsets and correlated to lower survival rates in pan-cancers. Targeting CH25H abrogated macrophage immunosuppressive function to enhance infiltrating T cell numbers and activation, which synergized with anti-PD-1 to improve anti-tumor efficacy. Mechanically, lysosome-accumulated 25HC competed with cholesterol for GPR155 binding to inhibit the kinase mTORC1, leading to AMPKα activation and metabolic reprogramming. AMPKα also phosphorylated STAT6 Ser564 to enhance STAT6 activation and ARG1 production. Together, we propose CH25H as an immunometabolic checkpoint, which manipulates macrophage fate to reshape CD8⁺ T cell surveillance and anti-tumor response.

01 May 2024·Pathology - Research and Practice

Circular RNA hsa_circ_0094976 modulates GPR155 to inhibit gastric adenocarcinoma malignant characteristics by targeting miR-223–3p

Article

Author: Yang, Yuhan ; Liu, Li ; Song, Lingli ; Li, Binxian ; Li, Xuefeng

BACKGROUNDThe abnormal expression of circular RNA (circRNA) has been confirmed to be closely related to the development of many human diseases including gastric adenocarcinoma (GA). This study aimed to elucidate the molecular mechanism and biological function of hsa_circ_0094976 (circ_0094976) in GA.METHODSThe expression of circ_0094976, miR-223-3p, and G protein-coupled receptor 155 (GPR155) mRNA was measured by quantitative real-time polymerase chain reaction. Cell viability, cell proliferation, colony formation, migration, and invasion were estimated by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay, colony formation assay, and transwell assay, respectively. The bioinformatics analysis, dual-luciferase reporter assay, and RNA pull-down assay were used for predicting and verifying the interaction of the circ_0094976/miR-223-3p/GPR155 axis. A xenograft mouse model was performed in nude mice to reveal the role of circ_0094976 in vivo.RESULTSCirc_0094976 was down-regulated in GA tissues and GA cell lines compared to normal controls. Overexpression of circ_0094976 inhibited the GA cell growth, migration, and invasion in vitro, and tumor growth in vivo. Circ_0094976 directly targeted miR-223-3p, and GPR155 was a direct target of miR-223-3p. Moreover, circ_0094976 sponging miR-223-3p to increase the expression of GPR155.CONCLUSIONWe disclosed that circ_0094976 could act as a sponge of miR-223-3p to regulate the expression of GPR155, and further restrain the development of GA, which may provide new insight into the therapy of GA.

16 Sep 2022·ScienceQ1 · CROSS-FIELD

Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1

Q1 · CROSS-FIELD

Article

Author: Stipp, Robin ; Samson, Nolwenn ; Nomura, Daniel K. ; Sugasawa, Yusuke ; Park, Eunyong ; Covey, Douglas F. ; Laplante, Mathieu ; Citron, Y. Rose ; Perera, Rushika M. ; Tribouillard, Laura ; Shin, Hijai R. ; Castaneda-Carpio, David ; Qian, Mingxing ; Goul, Claire S. ; Wang, Lei ; Davis, Oliver B. ; Evers, Alex S. ; Lim, Chun-Yan ; Jain, Aakriti ; Zoncu, Roberto

Lysosomes coordinate cellular metabolism and growth upon sensing of essential nutrients, including cholesterol. Through bioinformatic analysis of lysosomal proteomes, we identified lysosomal cholesterol signaling (LYCHOS, previously annotated as G protein–coupled receptor 155), a multidomain transmembrane protein that enables cholesterol-dependent activation of the master growth regulator, the protein kinase mechanistic target of rapamycin complex 1 (mTORC1). Cholesterol bound to the amino-terminal permease-like region of LYCHOS, and mutating this site impaired mTORC1 activation. At high cholesterol concentrations, LYCHOS bound to the GATOR1 complex, a guanosine triphosphatase (GTPase)–activating protein for the Rag GTPases, through a conserved cytoplasm-facing loop. By sequestering GATOR1, LYCHOS promotes cholesterol- and Rag-dependent recruitment of mTORC1 to lysosomes. Thus, LYCHOS functions in a lysosomal pathway for cholesterol sensing and couples cholesterol concentrations to mTORC1-dependent anabolic signaling.

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GPR155

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