A5101639918- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Protein Degradation and Inhibitors
- Neurotransmitter Receptor Influence on Behavior
- Computational Drug Discovery Methods
- Neurogenesis and neuroplasticity mechanisms
- Olfactory and Sensory Function Studies
- Protein Kinase Regulation and GTPase Signaling
- Biochemical Analysis and Sensing Techniques
- Neurobiology and Insect Physiology Research
- Photoreceptor and optogenetics research
- Cancer, Hypoxia, and Metabolism
- Amino Acid Enzymes and Metabolism
- Retinoids in leukemia and cellular processes
- Lipid metabolism and disorders
- Microtubule and mitosis dynamics
- Natural product bioactivities and synthesis
- Genetic and Environmental Crop Studies
- Legume Nitrogen Fixing Symbiosis
- Plant Diversity and Evolution
- Cassava research and cyanide
- Monoclonal and Polyclonal Antibodies Research
- Plant and Fungal Species Descriptions
- Autophagy in Disease and Therapy
Vanderbilt University
2013-2024
Hainan University
2014
Rockefeller University
1996-2001
Hengyang Academy of Agricultural Sciences
2000
Olfactory sensory neurons (OSNs) expressing a given odorant receptor (OR) gene project their axons to few specific glomeruli that reside at recognizable locations in the olfactory bulb. Connecting approximately 1000 populations of OSNs 1800 mouse bulb poses formidable wiring problem. Additional progress understanding mechanisms neuronal connectivity is dependent on knowing how these axonal pathways are organized and they form during development. Here we have applied genetic approach this We...
Vertebrate central nervous system (CNS) histogenesis depends on glia-guided migration of postmitotic neurons to form neuronal laminae. Previous studies have established that the protein astrotactin functions in murine cerebellar granule cell vitro. The gene encoding predicts a with three epidermal growth factor repeats and two fibronectin type III repeats. Astrotactin messenger RNA is expressed precursors cerebellum, hippocampus, cerebrum, olfactory bulb, where establishes laminar...
Arrestins were discovered for their role in homologous desensitization of G-protein-coupled receptors (GPCRs). Later non-visual arrestins shown to regulate several signaling pathways. Some these pathways require arrestin binding GPCRs, the regulation others is receptor independent. Here, we demonstrate that arrestin-3 binds E3 ubiquitin ligase parkin via multiple sites, preferentially interacting with its RING0 domain. Identification domains involved suggests likely relieves autoinhibition...
Arrestins bind active phosphorylated G protein-coupled receptors (GPCRs). Among the four mammalian subtypes, only arrestin-3 facilitates activation of JNK3 in cells. In available structures, Lys-295 lariat loop and its homologue Lys-294 arrestin-2 directly interact with activator-attached phosphates. We compared roles conformational equilibrium GPCR binding activation. Several mutants enhanced ability to GPCRs showed much lower activity towards JNK3, whereas a mutant that does not was more...
Abstract Arrestins demonstrate strong preference for phosphorylated over unphosphorylated receptors, but how arrestins “sense” receptor phosphorylation is unclear. A conserved lysine in the lariat loop of directly binds phosphate crystal structures activated arrestin‐1, ‐2, and ‐3. The supplies two negative charges to central polar core, which must be disrupted arrestin activation high‐affinity binding. Therefore, we hypothesized that receptor‐attached phosphates pull via this lysine, thus...
We tested the interactions with four different G protein-coupled receptors (GPCRs) of arrestin-3 mutants substitutions in loops, three which contact receptor structure arrestin-1-rhodopsin complex. Point mutations loop at distal tip N-domain (Glu157Ala), C-loop (Phe255Ala), back (Lys313Ala), and one finger (Gly65Pro) had mild variable effects on binding. In contrast, deletion Gly65 beginning reduced binding to all GPCRs tested, dopamine D2 being affected most dramatically. Thus, presence a...
Arrestins bind active phosphorylated G protein-coupled receptors (GPCRs). Among the four mammalian subtypes, only arrestin-3 facilitates activation of JNK3 in cells. In available structures, Lys-295 lariat loop and its homologue Lys-294 arrestin-2 directly interact with activator-attached phosphates. We compared role conformational equilibrium GPCR binding activation. Several mutants enhanced ability to GPCRs showed much lower activity towards JNK3, whereas a mutant that does not was more...
Arrestin-1, or visual arrestin, exhibits an exquisite selectivity for light-activated phosphorylated rhodopsin (P-Rh*) over its other functional forms. That is believed to be mediated by two well-established structural elements in the arrestin-1 molecule, activation sensor detecting active conformation of and phosphorylation responsive phosphorylation, which only can engage simultaneously. However, crystal structure arrestin-1-rhodopsin complex there are residues located close rhodopsin, do...
Abstract G protein‐coupled receptors (GPCRs) represent ∼30% of current drug targets. Ligand binding to these activates proteins and arrestins, which function in different signaling pathways. Given that functionally selective or biased ligands preferentially activate one two groups pathways, they may be superior medications for certain disease states. The identification such requires robust screening assays both protein arrestin activity. This unit describes protocols monitor reversible...
34 Background: Gastric cancer is the second most frequent cause of cancer-related death worldwide. We have previously shown that Dopamine and cAMP regulated phosphoprotein MW 32 kDa (DARPP-32) its truncated form (t-DARPP) are overexpressed in two-thirds gastric adenocarcinomas. Angiopoietin 2 (ANGPT2) -TIE2 signaling a secreted protein acts as key regulator adult vascular homeostasis blood vessel formation. Methods: The expression DARPP-32 multi-step carcinogenesis cascade was examined using...
ABSTRACT In rodents with unilateral ablation of the substantia nigra neurons supplying dopamine to striatum, chronic treatment precursor L-DOPA or agonists induces a progressive increase behavioral responses, process known as sensitization. The sensitization is blunted in arrestin-3 knockout mice. Using virus-mediated gene delivery dopamine-depleted striatum mice, we found that restoration fully rescued sensitization, whereas its mutant defective JNK activation did not. A 25-residue...
Arrestins are multifunctional proteins that were originally identified as suppressors of G protein‐coupled receptors signaling. Later arrestins found to serve adapter molecules bind numerous signaling proteins, such protein kinases, ubiquitin ligases, deubiquitinases, etc. Here, we showed the direct interaction with arrestin‐3 and parkin, which is a E3 ligase covalently attaches specific substrates, including mitochondrial proteins. Parkin essential for mitophagy – removal damaged...