A5064921157- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Protein Kinase Regulation and GTPase Signaling
- Sphingolipid Metabolism and Signaling
- Pancreatic function and diabetes
- Lipid Membrane Structure and Behavior
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Diabetes Treatment and Management
- Computational Drug Discovery Methods
- Mass Spectrometry Techniques and Applications
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Adenosine and Purinergic Signaling
- Nitric Oxide and Endothelin Effects
- Zebrafish Biomedical Research Applications
- Adipose Tissue and Metabolism
- Neuroendocrine regulation and behavior
- Lipid metabolism and biosynthesis
- Pharmacological Receptor Mechanisms and Effects
- Phagocytosis and Immune Regulation
- Mast cells and histamine
- Retinal Development and Disorders
- Pharmacological Effects and Assays
Tohoku University
2016-2025
Kyoto University
2024-2025
Kyoto Pharmaceutical University
2024-2025
New York University
2024
Columbia University
2024
Queen's University Belfast
2022-2024
The University of Tokyo
2006-2024
Kogakuin University
2024
Yasuda Women's University
2024
Okayama University
2024
Land plants evolved a long-distance transport system of water and nutrients composed the xylem phloem, both which are generated from procambium- cambium-comprising vascular stem cells. However, little is known about molecular mechanism cell communication governing xylem-phloem patterning. Here, we show that dodecapeptide (HEVHypSGHypNPISN; Hyp, 4-hydroxyproline), TDIF (tracheary element differentiation inhibitory factor), secreted phloem suppresses cells into through leucine-rich repeat...
G protein-independent, arrestin-dependent signaling is a paradigm that broadens the scope of protein-coupled receptors (GPCRs) beyond proteins for numerous biological processes. However, arrestin in collective absence functional has never been demonstrated. Here we achieve state "zero G" at cellular level using HEK293 cells depleted by CRISPR/Cas9 technology Gs/q/12 families Gα proteins, along with pertussis toxin-mediated inactivation Gi/o. Together lacking β-arrestins ("zero arrestin"),...
β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize protein signaling, initiate signaling on their own, and mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR-βarr complexes: the "tail" conformation, βarr primarily coupled phosphorylated GPCR C-terminal tail, "core" where, in addition is further engaged transmembrane core. However, relationship these distinct various functions βarrs unknown. Here, we created...
Abstract Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using multifaceted approach systematically characterize FR as inhibitor Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism action. We also use investigate whether inhibition Gq an effective...
The bioactive lysophospholipid mediator sphingosine-1-phosphate (S1P) promotes the egress of newly formed T cells from thymus and release immature B bone marrow. It has remained unclear, however, where how S1P is released. Here, we show that in mice, transporter spinster homolog 2 (Spns2) responsible for mature marrow, respectively. Global Spns2-KO mice exhibited marked accumulation thymi decreased numbers peripheral blood secondary lymphoid organs. Mature recirculating were reduced...
Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-coupled receptors, the GLP-1R undergoes agonist-mediated endocytosis, but functional therapeutic consequences of modulating endocytic trafficking have not been clearly defined. Here, we investigate a series biased agonists with variable propensities for internalization...
Ligand activation of β 2 -adrenergic receptors induces the phosphorylation kinase ERK in a β-arrestin–independent manner.
Two-thirds of human hormones and one-third clinical drugs act on membrane receptors that couple to G proteins achieve appropriate functional responses. While protein transducers from literature are annotated in the Guide Pharmacology database, two recent large-scale datasets now expand receptor-G ‘couplome’. However, these three differ scope reported couplings giving different coverage conclusions protein-coupled receptor (GPCR)-G signaling. Here, we report a common coupling map uncovering...
Signaling-biased ligands acting on G-protein-coupled receptors (GPCRs) differentially activate heterotrimeric G proteins and β-arrestins. Although a wealth of structural knowledge about signaling bias at the GPCR level exists (preferential engagement specific transducer), little is known transducer (different functions mediated by single partly due to poor understanding kinase (GRK)-mediated phosphorylation. Here, we reveal unique role Gq heterotrimer as determinant for GRK-subtype...
β-arrestins bind G protein-coupled receptors to terminate protein signaling and facilitate other downstream pathways. Using single-molecule fluorescence resonance energy transfer imaging, we show that β-arrestin is strongly autoinhibited in its basal state. Its engagement with a phosphopeptide mimicking phosphorylated receptor tail efficiently releases the from N domain assume distinct conformations. Unexpectedly, find binding receptor, phosphorylation barcode identical isolated...
The glucagon‐like peptide‐1 receptor (GLP‐1R) plays an important role in regulating insulin secretion and reducing body weight, making it a prominent target the treatment of type 2 diabetes obesity. Extensive research on GLP‐1R signaling has provided insights into connection between function physiological outcomes, such as correlation Gs secretion, yet exact mechanisms remain unclear. Here, we explore internalization pathway GLP‐1R, which is crucial for controlling release maintaining...