G Protein-Coupled Receptors in the Mammalian Blood-Brain Barrier

Abstract

The mammalian neurovascular unit (NVU) is comprised of neurons, glia, and vascular cells. The NVU is the nexus between the cardiovascular and central nervous system (CNS). The central component of the NVU is the blood-brain barrier (BBB) which consists of a monolayer of tightly connected endothelial cells covered by pericytes and further surrounded by astrocytic endfeet. In addition to preventing the diffusion of toxic species into the CNS, the BBB endothelium serves as a dynamic regulatory system facilitating the transport of molecules from the bloodstream to the brain and vis versa. The structural integrity and transport functions of the BBB are maintained, in part, by an orchestra of membrane receptors and transporters including members of the superfamily of G protein-coupled receptors (GPCRs). Here, we provide an overview of GPCRs known to regulate mammalian BBB structure and function and discuss how dysregulation of these pathways plays a role in various neurodegenerative diseases.

Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction

“…S1P is synthesized by phosphorylation of sphingosine derived from sphingolipids by sphingosine kinases 1 and 2 (Sphk1 and Sphk2). Intracellular S1P is secreted into the extracellular space via S1P transporters (e.g., Abca1 and Spns2) where it acts as an extracellular signaling molecule through GPCRs (S1PR1–5) coupled with G q , G i , G 12/13 , and Rho proteins ( Hao et al, 2020 ; Pluimer et al, 2020 ). S1P regulates a number of biological processes including vascular development and function.…”

Downregulation of TMEM220 Promotes Tumor Progression in Hepatocellular Carcinoma

“…Mechanism studies showed that overexpression of TMEM220 could regulate β-catenin and FOXO3 transcriptional activity by altering their subcellular localization, affecting the expression of downstream gene p21 and SNAIL, and ultimately reducing the progression of HCC.Conclusion: Altogether, our study proposes a working model in which upregulation of TMEM220 expression alters the genes expression involved in cell proliferation, thereby inhibiting HCC progression, which suggests that TMEM220 might serve as a clinical biomarker.Transmembrane protein 220 (TMEM220) is a family member of TMEMs that spans the entire width of the lipid bilayer and is permanently anchored. Many TMEMs from mammalian cells are well characterized in term of biological functions and structures [15][16][17][18], like G protein-coupled receptors (GPCR) [19][20][21], while the subcellular localization, physiological function and its role in cancer of TMEM220 remain blank. Recent studies reported LncRNAs TMEM220 is associated with HCC patients survival, and TMEM220 gene expression is downregulated in gastric cancer [22,23].…”

“…Transmembrane protein 220 (TMEM220) is a family member of TMEMs that spans the entire width of the lipid bilayer and is permanently anchored. Many TMEMs from mammalian cells are well characterized in term of biological functions and structures [15][16][17][18], like G protein-coupled receptors (GPCR) [19][20][21], while the subcellular localization, physiological function and its role in cancer of TMEM220 remain blank. Recent studies reported LncRNAs TMEM220 is associated with HCC patients survival, and TMEM220 gene expression is downregulated in gastric cancer [22,23].…”

Downregulation of TMEM220 promotes tumor progression in Hepatocellular Carcinoma

“…Mechanism studies showed that overexpression of TMEM220 could regulate β-catenin and FOXO3 transcriptional activity by altering their subcellular localization, affecting the expression of downstream gene p21 and SNAIL, and ultimately reducing the progression of HCC.Conclusion: Altogether, our study proposes a working model in which upregulation of TMEM220 expression alters the genes expression involved in cell proliferation, thereby inhibiting HCC progression, which suggests that TMEM220 might serve as a clinical biomarker.Transmembrane protein 220 (TMEM220) is a family member of TMEMs that spans the entire width of the lipid bilayer and is permanently anchored. Many TMEMs from mammalian cells are well characterized in term of biological functions and structures [15][16][17][18], like G protein-coupled receptors (GPCR) [19][20][21], while the subcellular localization, physiological function and its role in cancer of TMEM220 remain blank. Recent studies reported LncRNAs TMEM220 is associated with HCC patients survival, and TMEM220 gene expression is downregulated in gastric cancer [22,23].…”

“…Transmembrane protein 220 (TMEM220) is a family member of TMEMs that spans the entire width of the lipid bilayer and is permanently anchored. Many TMEMs from mammalian cells are well characterized in term of biological functions and structures [15][16][17][18], like G protein-coupled receptors (GPCR) [19][20][21], while the subcellular localization, physiological function and its role in cancer of TMEM220 remain blank. Recent studies reported LncRNAs TMEM220 is associated with HCC patients survival, and TMEM220 gene expression is downregulated in gastric cancer [22,23].…”