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Crystal Structure of a Lipid G Protein–Coupled Receptor
TLDR
The crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme in complex with an antagonist sphingolipid mimic provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P1, resulting in the modulation of immune and stromal cell responses. Expand
Sphingosine 1-Phosphate (S1P) Receptor Subtypes S1P1 and S1P3, Respectively, Regulate Lymphocyte Recirculation and Heart Rate*
TLDR
S 1P1-selective agonists will be of broad utility in understanding cell functions in vitro, and vascular physiology in vivo, and the success of the chemical approach for S1P1 suggests that selective tools for the resolution of function across this broad lipid receptor family are now possible. Expand
Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo
TLDR
Chemical modulation reveals differences in S1P-S1P1 'set points' among tissues and highlights both mechanistic advantages (lymphocyte sequestration) and risks (pulmonary edema) of therapeutic intervention. Expand
S1P1-selective in vivo-active agonists from high-throughput screening: off-the-shelf chemical probes of receptor interactions, signaling, and fate.
TLDR
SEW2871 recapitulates the action of S1P in all the signaling pathways examined and overlaps in interactions with key headgroup binding receptor residues, presumably replacing salt-bridge interactions with ion-dipole interactions. Expand
Full Pharmacological Efficacy of a Novel S1P1 Agonist That Does Not Require S1P-Like Headgroup Interactions
TLDR
Data show that CYM-5442 activates S1P1-dependent pathways in vitro and to levels of full efficacy in vivo through a hydrophobic pocket separate from the orthosteric site of S 1P binding that is headgroup-dependent. Expand
α-Synuclein Membrane Interactions and Lipid Specificity*
With the discovery of missense mutations (A53T and A30P) in α-synuclein (α-Syn) in several families with early onset familial Parkinson's disease, α-Syn aggregation and fibril formation have beenExpand
Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses
TLDR
Two-photon imaging of living T cells in explanted lymph nodes after treatment with S1P1 agonists or antagonists is provided and results provide visualization of transendothelial migration of T cells into lymphatic sinuses and suggest that S1E2 agonists act mainly on endothelial cell S1p1 receptors to inhibit lymphocyte migration. Expand
alpha-Synuclein membrane interactions and lipid specificity.
TLDR
The results suggest that alpha-Syn membrane interactions are physiologically important and the lipid composition of the cellular membranes may affect these interactions in vivo. Expand
Defective membrane interactions of familial Parkinson's disease mutant A30P alpha-synuclein.
TLDR
It is demonstrated that the familial Parkinson's disease-linked A30P mutant alpha-Syn is defective in binding to phospholipid vesicles in vitro as determined by vesicle ultracentrifugation, circular dichroism spectroscopy, and low-angle X-ray diffraction, which suggests that this species could be a physiologically relevant and functional entity. Expand
Presenilin mutations associated with Alzheimer disease cause defective intracellular trafficking of β-catenin,a component of the presenilin protein complex
TLDR
It is reported here that presenilin mutations associated with familial Alzheimer disease (but not the non–pathogenic Glu318Gly polymorphism) alter the intracellular trafficking of β-catenin after activation of the Wnt/β- catenin signal transduction pathway. Expand
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