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At least 811 records · Page 45Linked to original sources
PubMed2005

Tryptophan residues flanking the second transmembrane helix (TM2) set the signaling state of the Tar chemoreceptor.

The chemoreceptors of Escherichia coli are homodimeric membrane proteins that cluster in patches near the cell poles. They convert environmental stimuli into intracellular signals that control flagellar rotation. The functional domains of a receptor are physically separated by the cell membrane. Chemoeffectors bind to the extracellular (periplasmic) domain, and the cytoplasmic domain mediates signaling and adaptation. These two domains communicate through the second transmembrane helix (TM2) that connects them. In the high-abundance receptors Tar and Tsr, TM2 is flanked by tryptophan residues, which should localize preferentially to the interfacial zone between the polar and hydrophobic layers of the phospholipid bilayer. To investigate the functional significance of the Trp residues that flank TM2 of Tar, we used site-directed mutagenesis to generate the W192A and W209A substitutions. The W192A protein retains full activity in vivo and in vitro, but it increases the K(i) for aspartate in the in vitro assay 3-fold. The W209A replacement eliminates receptor-mediated stimulation of CheA in vitro, and it leads to an increased level of adaptive methylation in vivo. This phenotype in some respects mimics the changes seen upon binding aspartate. Since the W209A substitution may cause the C-terminus of TM2 to protrude farther into the cytoplasm, these results reinforce the hypothesis that aspartate binding causes a similar displacement. Moving Trp to each position from residue 206 to residue 212 generated a wide variety of Tar signaling states that are generally consistent with the predictions of the piston model of transmembrane signaling. None of these receptors was completely locked in one signaling mode, although most showed pronounced signaling biases. Our findings suggest that the Trp residues flanking TM2, especially Trp-209, are important in setting the baseline activity and ligand sensitivity of the Tar receptor. We also conclude that the Tyr-210 residue plays at least an auxiliary role in this control.

Alanine↗
PubMed2005

Cooperative signaling among bacterial chemoreceptors.

Four chemoreceptors in Escherichia coli mediate responses to chemicals in the environment. The receptors self-associate and localize to the cell poles. This aggregation implies that interactions among receptors are important parameters of signal processing during chemotaxis. We examined this phenomenon using a receptor-coupled in vitro assay of CheA kinase activity. The ability of homogeneous populations of the serine receptor Tsr and the aspartate receptor Tar to stimulate CheA was directly proportional to the ratio of the receptor to total protein in cell membranes up to a fraction of 50%. Membranes containing mixed populations of Tar and Tsr supported an up to 4-fold greater stimulation of CheA than expected on the basis of the contributions of the individual receptors. Peak activity was seen at a Tar:Tsr ratio of 1:4. This synergy was observed only when the two proteins were expressed simultaneously, suggesting that, under our conditions, the fundamental "cooperative receptor unit" is relatively static, even in the absence of CheA and CheW. Finally, we observed that inhibition of receptor-stimulated CheA activity by serine or aspartate required significantly higher concentrations of ligand for membranes containing mixed Tsr and Tar populations than for membranes containing only Tsr (up to 10(2)-fold more serine) or Tar (up to 10(4)-fold more aspartate). Together with recent analyses of the interactions of Tsr and Tar in vivo, our results reveal the emergent properties of mixed receptor populations and emphasize their importance in the integrated signal processing that underlies bacterial chemotaxis.

Aspartic Acid↗
PubMedDate not supplied

Intact chemoreceptor-based biosensors.

A receptrode biosensor is presented that uses intact chemoreceptor-based molecular recognition from antennular structures of the Hawaiian swimming crab species Portunis sanguinolentus. The sensor is coupled to a learning, pattern recognition calculation for performing analytical chemistry. Action potential waveforms are used to establish the identity of individual action potential types that can be associated to particular analytes. The pattern recognition calculations used are referred to as cluster analysis (CA) and principal component analysis (PCA). Action potential similarities are determined by using a dendrogram plot of the cluster analysis results and further elucidated by using principal component scores plots. Quantitative analysis was performed after classification of analyte and background responses. Chemoresponses to salinity and trimethylamine N-oxide, two chemical constituents that are found in the crustacean living environment, were investigated and gave analytic responses over several orders of magnitude.

Action Potentials↗
PubMedDate not supplied

Studies of chemoreceptor perception in mollusks.

The formation and operation of the peripheral nervous system can be observed and studied in mollusks using as an example the primitive chemoreceptor organ, the osphradium, which is connected to the visceral arch of the CNS and analyzes the physicochemical properties of water in the mantle cavity. Nerve recordings showed that the osphradium is sensitive to excess osmotic pressure, sodium chloride, and amino acids. In addition, the osphradium responds to the quality of the water in which the animal is living. The osphradium of the pond snail retains its ancient multisensory function, uniting the perception of various chemical and physical stimuli. Patch clamp recordings at fixed potential or current were used to study membrane currents in identified ganglion and receptor cells, associated with increases in the concentrations of Na+ and L-aspartate in the solution bathing the osphradium. The influx current appears to be a sodium and/or calcium current, and is not blocked by tetraethylammonium, while the efflux current is a potassium current, as has been shown for the taste cells of vertebrates.

Animals↗
PubMedDate not supplied

Structure of the serine chemoreceptor in Escherichia coli.

Many biological processes depend on the function of proteins that detect changes in a cell's environment and transmit the information to the cytoplasm, for example, peptide hormone receptors. In Escherichia coli this class of proteins is exemplified by the sensory transducers (also called signalling proteins or methyl-accepting chemotaxis proteins) which have a central role in mediating chemotactic behaviour. The sensory transducers are the products of four genes: tsr, tar, tap and trg. Each transducer detects changes in the environmental concentration of one or a very few attractants: Tsr, serine; Tar, aspartate and maltose; Tap, unknown; and Trg, ribose and galactose. Tsr and Tar act directly as chemoreceptors for the amino acid attractants and signal changes in their degree of occupancy to the flagellar apparatus. Detection of these changes in occupancy is made possible as the transducers are methylated at multiple glutamate residues such that their level of methylation reflects the most recent chemoeffector concentration. Biochemical and genetic information concerning the serine transducer protein has been accumulating rapidly but little is known about the structure of the molecule. We present here the nucleotide sequence of the tsr gene of E. coli; the amino acid sequence derived from it suggests that the Tsr transducer protein has a relatively simple transmembrane structure that may place limits on the mechanisms available for the transmission of sensory information into the cell.

Amino Acid Sequence↗
PubMed2003

Midbrain serotonergic neurons are central pH chemoreceptors.

Serotonergic neurons in the medulla are central respiratory chemoreceptors. Here we show that serotonergic neurons in the midbrain of rats are also highly chemosensitive to small changes in CO2/pH and are closely associated with large penetrating arteries. We propose that midbrain raphé neurons are sensors of blood CO2 that maintain pH homeostasis by inducing arousal, anxiety and changes in cerebrovascular tone in response to respiratory acidosis.

Action Potentials↗
PubMed2006

KIN-29 SIK regulates chemoreceptor gene expression via an MEF2 transcription factor and a class II HDAC.

The expression of individual chemoreceptor (CR) genes in Caenorhabditis elegans is regulated by multiple environmental and developmental cues, possibly enabling C. elegans to modulate its sensory responses. We had previously shown that KIN-29, a member of the salt-inducible kinase family, acts in a subset of chemosensory neurons to regulate the expression of CR genes, body size and entry into the alternate dauer developmental stage. Here, we show that KIN-29 regulates these processes by phosphorylating the HDA-4 class II histone deacetylase (HDAC) and inhibiting the gene repression functions of HDA-4 and an MEF-2 MADS domain transcription factor. MEF-2 binds directly to the CR gene regulatory sequences, and is required only to repress but not activate CR gene expression. A calcineurin phosphatase antagonizes the KIN-29/MEF-2-regulated pathway to modulate levels of CR gene expression. Our results identify KIN-29 as a new regulator of MEF2/HDAC functions in the nervous system, reveal cell-specific mechanisms of action of this pathway in vivo and demonstrate remarkable complexity in the regulation of CR gene expression in C. elegans.

Animals↗
PubMed1975

The role of baroreceptors and chemoreceptors in the regulation of the cerebral circulation.

1. Ten experiments, each using two dogs, were performed to evaluate the effect of chemoreceptor and baroreceptor activity on the cerebral circulation. 2. The carotid bifurcation areas were vascularly isolated bilaterally and perfused with arterial blood from a second animal. 3. Bilateral vagotomy interrupted stimuli from the aortic group of receptors. 4. Administration of 5% carbon dioxide to the donor animal resulted in an increase in cerebral (cortical) blood flow in the recipient. 5. A change in the arterial perfusion pressure from the donor resulted in a reciprocal change in the cerebral blood flow of the recipient. These changes were abolished by sectioning the sinus nerves.

Animals↗
PubMed1998

A mechanism for simultaneous sensing of aspartate and maltose by the Tar chemoreceptor of Escherichia coli.

The Tar chemoreceptor of Escherichia coli exhibits partial sensory additivity. Tar can mediate simultaneous responses to two disparate ligands, aspartate and substrate-loaded maltose-binding protein (MBP). To investigate how one receptor generates concurrent signals to two stimuli, ligand-binding asymmetry was imposed on the rotationally symmetric Tar homodimer. Mutations causing specific defects in aspartate or maltose chemotaxis were introduced pairwise into plasmid-borne tar genes. The doubly mutated tar genes did not restore aspartate or maltose chemotaxis in a strain containing a chromosomal deletion of tar (delta tar). However, when Tar proteins with complementing sets of mutations were co-expressed from compatible plasmids, the resulting heterodimeric receptors enabled delta tar cells to respond to aspartate or maltose. The effect of one attractant on the response to the other depended on the relative orientations of the functional binding sites for aspartate and MBP. When the sites were in the 'same' orientation, saturating levels of one attractant strongly inhibited chemotaxis to the other. In the 'opposite' orientation, such inhibitory effects were negligible. These data demonstrate that opposing subunits of Tar can transmit signals to aspartate and maltose independently if the ligands are restricted to the 'opposite' binding orientation. When aspartate and MBP bind in the 'same' orientation, they compete for signalling through one subunit. In the wild-type Tar dimer, aspartate and MBP can bind in either the 'same' or the 'opposite' orientation, a freedom that can explain the partial additivity of the aspartate and maltose responses that is seen with tar+ cells.

ATP-Binding Cassette Transporters↗
PubMed2000

The aspartate chemoreceptor Tar is effectively methylated by binding to the methyltransferase mainly through hydrophobic interaction.

In the chemotaxis of Escherichia coli, adaptation requires the methylation and demethylation of transmembrane receptors, which are catalysed by the methyltransferase CheR and the methylesterase CheB respectively. CheR binds to major chemoreceptors through their C-terminal motif NWETF, which is distinct from the methylation sites. In this study, we carried out a systematic mutagenesis of the pentapeptide sequence of Tar. Receptor methylation and adaptation were severely impaired by the alanine substitution of residue W550 and, to a lesser extent, by that of F553. Substitution of residues N549, E551 and T552 had only a slight or little effect. The defects of the W550A and F553A mutations were suppressed by high- and low-level overproduction of CheR respectively. Expression of a fusion protein containing the NWETF sequence, but not its W550A and F553A versions, inhibited chemotaxis of the Che+ strain. In an in vitro assay, CheR bound to the wild-type version but not to the mutant versions. These results and further mutagenesis suggest that the hydrophobicity and the size of residues W550 and F553 are critical in the interaction with CheR, a conclusion that is consistent with the crystal structure of a CheR-NWETF complex. On the other hand, the negatively charged side chain of E551 and the polar side chains of N549 and T552 may not be strictly required, although the presence of a salt bridge and hydrogen bonds between these residues and residues from CheR has been noted in the co-crystal.

Aspartic Acid↗
PubMed1997

Dopaminergic properties of cultured rat carotid body chemoreceptors grown in normoxic and hypoxic environments.

Using dissociated carotid body (CB) cultures prepared from neonatal (postnatal days 5-7; P7) or juvenile (postnatal day 19-20; P20) rats, we compared catecholaminergic properties and mechanisms of O2 sensing in glomus cells grown in normoxic (Nox; 20% O2) and chronically hypoxic (CHox; 6% O2) environments for up to 2 weeks. In Nox cultures, basal dopamine (DA) release, determined by HPLC and normalized to the number of tyrosine hydroxylase-positive glomus cells present, was similar for P7 and P20 cultures (approximately 0.3 pmol/1,000 cells/15 min) and was unaffected by culture duration (2 vs. 12 days). Acute hypoxia (5 and 10% O2) caused a dose-dependent stimulation (6x and 3x basal, respectively) in DA release, that was inhibited by nifedipine (10 microM). DA release was also stimulated by high extracellular K+ (30 mM) and iberiotoxin (200 nM), a selective blocker of PO2-regulated, Ca-dependent K+ channel in glomus cells. The stimulatory effect of iberiotoxin was similar to 5% O2 in P20 cultures, but substantially less (about one-half) in P7 cultures. In contrast, in CHox cultures, basal DA release was substantially elevated, approximately 8x Nox levels, although this did not correlate with significant differences in stores. Further, whereas acute hypoxia (5% O2) and high K+ also stimulated DA release in CHox cultures (approximately 2x and approximately 3x basal), iberiotoxin (200 nM) did not. Thus, after chronic hypoxia in vitro, there is an enhanced basal catecholamine release and an apparent down-regulation of functional Ca-dependent K+ channels in CB chemoreceptors. These cellular adaptations may relate to changes in CB chemosensitivity during chronic hypoxemia.

Animals↗
PubMed2001

Pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEB): chemoreceptors and regulators of lung development.

The airway and alveolar epithelia contain pulmonary neuroendocrine cells whose structure indicates an endocrine function. They are also in contact with sensory nerve fibres. These cells often aggregate into distinct corpuscles-neuroepithelial bodies-and carry membrane receptors sensitive to a number of stimuli, including hypoxia and nicotine. They synthesise, store and release a number of bioactive substances such as serotonin, calcitonin gene-related peptide and the mitogen bombesin. When these are released they contribute to redistribution of pulmonary blood flow, regulation of bronchomotor tone, modulation of the immune response, stimulation of sensory nerve fibres and regulation of lung growth and development. Pulmonary neuroendocrine cells and neuroepithelial bodies seem to be most important in the fetal and neonatal lung as regulators of airway development and hypoxia-sensitive chemoreceptors. There is a link between these cells and specific types of lung cancer and their involvement in lung and paediatric pathology may be profound.

Animals↗
PubMed2004

Interlocus nonrandom association of polymorphisms in Drosophila chemoreceptor genes.

Some forms of multilocus selection with epistasis, such as truncation selection, can effectively reduce the mutation load [Kondrashov, A. S. (1988) Nature 336, 435-440]. Many quantitative characters, including complex genetic diseases, are likely to be subject to these types of selection. However, direct measurement of selection in natural populations is difficult and the effect of epistasis on within-species variations remains unclear. Epistatic interaction in the fitness effect can generate linkage disequilibrium (LD). Therefore, we may detect the action of natural selection from its amount and pattern. Here, we report a large number of interlocus nonrandom associations between polymorphisms in 98 Drosophila chemoreceptor genes. LD was examined in two fly samples collected at the same location, but in different seasons. The amount of LD was much larger in the spring sample than in the autumn one. The between-sample difference was much more striking for the replacement polymorphisms than for the silent polymorphisms. This difference between the replacement and silent polymorphisms could not be attributed to differences in the mean marker distances. We also found a significant excess of associations between one frequent and one less common allele for the replacement polymorphisms, but not for the silent polymorphisms. It is unlikely that a simple seasonal bottleneck could explain all these differences in the scale of LD between the samples and between the replacement and silent polymorphisms. Natural selection is suggested to play a significant role in shaping the pattern of LD observed in this study.

Alleles↗
PubMed2005

Adaptive evolution in the SRZ chemoreceptor families of Caenorhabditis elegans and Caenorhabditis briggsae.

We investigated the possibility of positive selection acting on members of the putative seven-pass chemoreceptor superfamily in Caenorhabditis elegans, which comprises approximately 1,300 genes encoding seven-pass G protein-coupled receptors (GPCRs). Using a maximum-likelihood approach, we conducted statistical tests for evidence of codon sites where the ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site (d(N)/d(S)) was >1. Evidence for positive selection was found only for the srz family, about which virtually nothing specific is known. We extended the annotation of the srz gene family, establishing gene models for 60 srz genes in C. elegans and 28 srz genes in Caenorhabditis briggsae. d(N)/d(S) ratios varied dramatically in different regions of the SRZ proteins, peaking in predicted extracellular regions. These regions included 23 sites where evidence of positive selection was highly significant, corresponding remarkably well with regions implicated in ligand binding in other GPCR family members. We interpret these results as indicating that the srz family is under positive selection, probably driven by ligand binding.

Adaptation, Physiological↗
PubMed2003

Quantitative modeling of sensitivity in bacterial chemotaxis: the role of coupling among different chemoreceptor species.

We propose a general theoretical framework for modeling receptor sensitivity in bacterial chemotaxis, taking into account receptor interactions, including those among different receptor species. We show that our model can quantitatively explain the recent in vivo measurements of receptor sensitivity at different ligand concentrations for both mutant and wild-type strains. For mutant strains, our model can fit the experimental data exactly. For the wild-type cell, our model is capable of achieving high gain while having modest values of Hill coefficient for the response curves. Furthermore, the high sensitivity of the wild-type cell in our model is maintained for a wide range of ambient ligand concentrations, facilitated by near-perfect adaptation and dependence of ligand binding on receptor activity. Our study reveals the importance of coupling among different chemoreceptor species, in particular strong interactions between the aspartate (Tar) and serine (Tsr) receptors, which is crucial in explaining both the mutant and wild-type data. Predictions for the sensitivity of other mutant strains and possible improvements of our model for the wild-type cell are also discussed.

Bacterial Proteins↗
PubMed1975

Chemoreceptors and feeding in calanoid copepods (Arthropoda: Crustacea).

Ultrastructural studies of the mouthparts of the calanoid copepod Diaptomus pallidus have revealed the presence of numerous chemoreceptors, and the apparent absence of mechanoreceptors. The setae contain no muscles, and the setules are noncellular extensions of their chitin wall. This allows a new insight into the selective feeding of zooplankters.

Animals↗
PubMed1986

Analysis of mutations in the transmembrane region of the aspartate chemoreceptor in Escherichia coli.

Site-specific mutagenesis was used to replace an alanine with a lysine residue and to create a deletion of seven amino acids into the first transmembrane region (TMI region) of the aspartate chemoreceptor in Escherichia coli. The mutations resulted in the loss of aspartate chemotaxis on tryptone motility plates. However, both mutant proteins were able to associate with the membrane and to bind aspartate. They were both refractory to methylation or to modification of the C-terminal region of the protein by the cheB gene product. These results suggested that the integrity of the TMI domain of the protein was required to maintain the function of the cytoplasmic portion of the receptor. The Lys-19 mutant retained the ability to generate a repellent response. Analysis of suppressor mutations of the Lys-19 mutation suggested that formation of an ion pair or specific changes in a 40 amino acid stretch in the cytoplasmic region of the protein (from amino acid 264 to amino acid 303) could suppress the effects of the Lys-19 mutation. The TMI region of the protein may be involved in transmembrane transmission of signals from the periplasmic portion of the cell to the cytoplasmic portion of the Tar protein.

Amino Acid Sequence↗
PubMed1998

Intersubunit interaction between transmembrane helices of the bacterial aspartate chemoreceptor homodimer.

The transmembrane domain that connects the extracellular and intracellular domains of cell-surface receptors must play a critical role in signal transduction. Here, we report studies of the interaction between the transmembrane helices (TM1 and TM2) of the Escherichia coli aspartate chemoreceptor (Tar). Tar exists as a homodimer regardless of its state of ligand occupancy. A particular residue substitution in TM1 (A19K) abolishes the signaling ability of Tar. This signaling defect can be suppressed by single residue substitutions in TM2 (W192R, A198E, V201E, and V202L). We have found that these suppressors can be divided into two groups. A198E and V201E (class 1) almost completely suppress the defects caused by A19K, and this suppression occurs between two subunits of the Tar dimer. In contrast, W192R and V202L (class 2) fail to suppress some signaling defects, and their suppression does not occur between subunits. Because disulfide-crosslinking studies predict that residues 198 and 201 point toward residue 19 of the partner subunit, we propose that the class 1 suppressors form an intersubunit salt bridge with Lys-19. Indeed, A19K was suppressed by several additional aspartate or glutamate substitutions on the same face of TM2 occupied by residues 198 and 201. None of these intersubunit salt bridges perturb signaling function, suggesting that the mechanism of transmembrane signal propagation does not involve large displacements (such as extensive rotation) of the TM1 and TM2 helices relative to each other.

Amino Acid Substitution↗