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Receptor

About: Receptor is a research topic. Over the lifetime, 159318 publications have been published within this topic receiving 8299881 citations.


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Journal ArticleDOI
TL;DR: It is shown that LPS is cross-linked specifically to TLR4 and MD-2 only when co-expressed with CD14, and contention that L PS is in close proximity to the three known proteins of its membrane receptor complex is supported.

673 citations

Journal ArticleDOI
TL;DR: This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.
Abstract: Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

673 citations

Journal ArticleDOI
TL;DR: It is suggested that AMPA receptor peak response open probability can be increased by PKA through phosphorylation of GluR1 Ser845.
Abstract: Modulation of postsynaptic AMPA receptors in the brain by phosphorylation may play a role in the expression of synaptic plasticity at central excitatory synapses. It is known from biochemical studies that GluR1 AMPA receptor subunits can be phosphorylated within their C terminal by cAMP-dependent protein kinase A (PKA), which is colocalized with the phosphatase calcineurin (i.e., phosphatase 2B). We have examined the effect of PKA and calcineurin on the time course, peak open probability ( P O,PEAK ), and single-channel properties of glutamateevoked responses for neuronal AMPA receptors and homomeric GluR1(flip) receptors recorded in outside-out patches. Inclusion of purified catalytic subunit Cα-PKA in the pipette solution increased neuronal AMPA receptor P O,PEAK (0.92) compared with recordings made with calcineurin included in the pipette ( P O,PEAK 0.39). Similarly, Cα-PKA increased P O,PEAK for recombinant GluR1 receptors (0.78) compared with patches excised from cells cotransfected with a cDNA encoding the PKA peptide inhibitor PKI ( P O,PEAK 0.50) or patches with calcineurin included in the pipette ( P O,PEAK 0.42). Neither PKA nor calcineurin altered the amplitude of single-channel subconductance levels, weighted mean unitary current, mean channel open period, burst length, or macroscopic response waveform for recombinant GluR1 receptors. Substitution of an amino acid at the PKA phosphorylation site (S845A) on GluR1 eliminated the PKA-induced increase in P O,PEAK , whereas the mutation of a Ca 2+ ,calmodulin-dependent kinase II and PKC phosphorylation site (S831A) was without effect. These results suggest that AMPA receptor peak response open probability can be increased by PKA through phosphorylation of GluR1 Ser845.

673 citations

Journal ArticleDOI
23 Nov 2006-Nature
TL;DR: Two discrete binding sites in the GABAA receptor’s transmembrane domains are identified that mediate the potentiating and direct activation effects of neurosteroids and provide a unique opportunity for the development of new therapeutic, neurosteroid-based ligands and transgenic disease models of Neurosteroid dysfunction.
Abstract: Inhibitory neurotransmission mediated by GABA(A) receptors can be modulated by the endogenous neurosteroids, allopregnanolone and tetrahydro-deoxycorticosterone(1). Neurosteroids are synthesized de novo in the brain during stress(2), pregnancy(3) and after ethanol consumption(4), and disrupted steroid regulation of GABAergic transmission is strongly implicated in several debilitating conditions such as panic disorder, major depression, schizophrenia, alcohol dependence and catamenial epilepsy(3,5-8). Determining how neurosteroids interact with the GABA(A) receptor is a prerequisite for understanding their physiological and pathophysiological roles in the brain. Here we identify two discrete binding sites in the receptor's transmembrane domains that mediate the potentiating and direct activation effects of neurosteroids. They potentiate GABA responses from a cavity formed by the alpha-subunit transmembrane domains, whereas direct receptor activation is initiated by interfacial residues between alpha and beta subunits and is enhanced by steroid binding to the potentiation site. Thus, significant receptor activation by neurosteroids relies on occupancy of both the activation and potentiation sites. These sites are highly conserved throughout the GABA(A) receptor family, and their identification provides a unique opportunity for the development of new therapeutic, neurosteroid-based ligands and transgenic disease models of neurosteroid dysfunction.

673 citations

Journal ArticleDOI
04 Aug 1988-Nature
TL;DR: This work has investigated the ability of each subtype to regulate PI hydrolysis and adenylyl cyclase when expressed individually in a cell lacking endogenous mAChRs and results indicate that the different receptor subtypes are functionally specialized.
Abstract: Muscarinic acetylcholine receptors (mAChRs), like many other neurotransmitter and hormone receptors, transduce agonist signals by activating G proteins to regulate ion channel activity and the generation of second messengers via the phosphoinositide (PI) and adenylyl cyclase systems. Human mAChRs are a family of at least four gene products which have distinct primary structures, ligand-binding properties and patterns of tissue-specific expression. To examine the question of whether functional differences exist between multiple receptor subtypes, we have investigated the ability of each subtype to regulate PI hydrolysis and adenylyl cyclase when expressed individually in a cell lacking endogenous mAChRs. We show that the HM2 and HM3 mAChRs efficiently inhibit adenylyl cyclase activity but poorly activate PI hydrolysis. In contrast, the HM1 and HM4 mAChRs strongly activate PI hydrolysis, but do not inhibit adenylyl cyclase, and in fact can substantially elevate cAMP levels. Interestingly, the subtypes that we find to be functionally similar are also more similar in sequence. Our results indicate that the different receptor subtypes are functionally specialized.

673 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
20234,222
20226,323
20213,048
20203,388
20193,290