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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
Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection
TLDR
It is demonstrated that suppression of early innate immune responses through S1P1 signaling results in reduced mortality during infection with a human pathogenic strain of influenza virus, suggesting that diseases in which amplification of cytokine storm is a significant pathological component could be chemically tractable. Expand
Piezo1, a mechanically activated ion channel, is required for vascular development in mice
TLDR
It is demonstrated that Piezo1 is activated by shear stress, the major type of mechanical force experienced by endothelial cells in response to blood flow, which suggests a potential role forPiezo1 in mechanotransduction in adult cardiovascular function and disease. Expand
Piezo1 links mechanical forces to red blood cell volume
TLDR
It is shown that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression, which plays an essential role in RBC volume homeostasis. Expand
LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength
TLDR
It is demonstrated that LRRC8 proteins together constitute the VRAC pore and that hypotonic stress can activate VRAC through a decrease in cytoplasmic Γ, and that low ionic strength in the absence of an osmotic gradient activates the complexes in bilayers. Expand
Dehydrated Hereditary Stomatocytosislinked to gain-of-function mutations in mechanically activated PIEZO1 ion channels
TLDR
It is found that all PIEZO1 mutations give rise to mechanically activated currents that inactivate more slowly than wild-type currents, providing insight that helps to explain the increased permeability of cations in RBCs of DHS patients. Expand
Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia
TLDR
This work identifies biallelic mutations in PIEZO1 (a splicing variant leading to early truncation and a non-synonymous missense variant) in a pair of siblings affected with persistent lymphoedema caused by congenital lymphatic dysplasia and delineates a novel clinical category of PIEzO1-associated hereditary lymphOedema. Expand
Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection
TLDR
A mouse model of hereditary xerocytosis is engineered and it is shown that Plasmodium infection fails to cause experimental cerebral malaria in these mice due to the action of Piezo1 in RBCs and in T cells. Expand
OSCA/TMEM63 are an evolutionarily conserved family of mechanically activated ion channels
TLDR
It is conclusively demonstrated that OSCA1.2, one of the Arabidopsis thaliana O SCA proteins, is an inherently mechanosensitive, pore-forming ion channel. Expand
Correction: Corrigendum: Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels
TLDR
In the first paragraph of the Methods section in this Article, case 8 (K8 in Table 1) was incorrectly referred to as case 4 and the following is the correct sentence: ‘Case 8 (ref. 3) and family 3 were case reports, these patients expressed a moderate form of anaemia and haemolysis without initial evidence of perinatal oedema or pseudohyperkalaemia. Expand
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