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At least 865 records · Page 48Linked to original sources
PubMed1973

Acetylcholine: fast axoplasmic transport in insect chemoreceptor fibers.

Acetylcholine is transported along insect chemoreceptor axons at a rate of 12 to 13 centimeters per day after peripheral uptake of choline. Colchicine, vinblastine sulfate, and cytochalasin B all block transport, but transport continues in axons separated surgically from the cell body. These data from an insect are in accord with many studies on vertebrates which have implicated intracellular microtubules in the transport mechanism. The peripheral uptake of choline and its acetylation and transport to nerve terminals in the brain are consistent withthe suggestion that acetylcholine is an antennal sensory transmitter in insects.

Acetylcholine↗
PubMed1988

Chemotransduction in the carotid body: K+ current modulated by PO2 in type I chemoreceptor cells.

The ionic currents of carotid body type I cells and their possible involvement in the detection of oxygen tension (Po2) in arterial blood are unknown. The electrical properties of these cells were studied with the whole-cell patch clamp technique, and the hypothesis that ionic conductances can be altered by changes in PO2 was tested. The results show that type I cells have voltage-dependent sodium, calcium, and potassium channels. Sodium and calcium currents were unaffected by a decrease in PO2 from 150 to 10 millimeters of mercury, whereas, with the same experimental protocol, potassium currents were reversibly reduced by 25 to 50 percent. The effect of hypoxia was independent of internal adenosine triphosphate and calcium. Thus, ionic conductances, and particularly the O2-sensitive potassium current, play a key role in the transduction mechanism of arterial chemoreceptors.

Animals↗
PubMed1996

Signaling by the Escherichia coli aspartate chemoreceptor Tar with a single cytoplasmic domain per dimer.

Many transmembrane receptors are oligomeric proteins. Binding of a ligand may alter the oligomeric state of the receptor, induce structural changes within the oligomer, or both. The bacterial aspartate chemoreceptor Tar forms a homodimer in the presence or absence of ligands. Tar mediates attractant and repellent responses by modulating the activity of the cytoplasmic kinase CheA. In vivo intersubunit suppression was used to show that certain combinations of full-length and truncated mutant Tar proteins complemented each other to restore attractant responses to aspartate. These results suggest that heterodimers with only one intact cytoplasmic domain are functional. The signaling mechanism may require interactions between dimers or conformational changes within a single cytoplasmic domain.

Aspartic Acid↗
PubMed1996

Attractant signaling by an aspartate chemoreceptor dimer with a single cytoplasmic domain.

Signal transduction across cell membranes often involves interactions among identical receptor subunits, but the contribution of individual subunits is not well understood. The chemoreceptors of enteric bacteria mediate attractant responses by interrupting a phosphotransfer circuit initiated at receptor complexes with the protein kinase CheA. The aspartate receptor (Tar) is a homodimer, and oligomerized cytoplasmic domains stimulate CheA activity much more than monomers do in vitro. Intragenic complementation was used to show in Escherichia coli that heterodimers containing one full-length and one truncated Tar subunit mediated responses to aspartate in the presence of full-length Tar homodimers that could not bind aspartate. Thus, a Tar dimer containing only one cytoplasmic domain can initiate an attractant (inhibitory) signal, although it may not be able to stimulate kinase activity of CheA.

Aspartic Acid↗
PubMed1998

Molecular cloning, sequencing, and expression of a chemoreceptor gene from Leptospirillum ferrooxidans.

We have cloned and sequenced a 2,262-bp chromosomal DNA fragment from the chemolithoautotrophic acidophilic bacterium Leptospirillum ferrooxidans. This DNA contained an open reading frame for a 577-amino-acid protein showing several characteristics of the bacterial chemoreceptors and, therefore, we named this gene lcrI for Leptospirillum chemotaxis receptor I. This is the first sequence reported for a gene from L. ferrooxidans encoding a protein. The lcrI gene showed both sigma 28-like and sigma 70-like putative promoters. The LcrI deduced protein contained two hydrophobic regions most likely corresponding to the two transmembrane regions present in all of the methyl-accepting chemotaxis proteins (MCPs) which make them fold with both periplasmic and cytoplasmic domains. We have proposed a cytoplasmic domain for LcrI, which also contains the highly conserved domain (HCD region), present in all of the chemotactic receptors, and two probable methylation sites. The in vitro expression of a DNA plasmid containing the 2,262-bp fragment showed the synthesis of a 58-kDa protein which was immunoprecipitated by antibodies against the Tar protein (an MCP from Escherichia coli), confirming some degree of antigenic conservation. In addition, this 58-kDa protein was expressed in E. coli, being associated with its cytoplasmic membrane fraction. It was not possible to determine a chemotactic receptor function for LcrI expressed in E. coli. This was most likely due to the fact that the periplasmic pH of E. coli, which differs by 3 to 4 pH units from that of acidophilic chemolithotrophs, does not allow the right conformation for the LcrI periplasmic domain.

Amino Acid Sequence↗
PubMed2006

Differential activation of Escherichia coli chemoreceptors by blue-light stimuli.

Enteric bacteria tumble, swim slowly, and are then paralyzed upon exposure to 390- to 530-nm light. Here, we analyze this complex response in Escherichia coli using standard fluorescence microscope optics for excitation at 440 +/- 5 nm. The slow swimming and paralysis occurred only in dye-containing growth media or buffers. Excitation elicited complete paralysis within a second in 1 muM proflavine dye, implying specific motor damage, but prolonged tumbling in buffer alone. The tumbling half-response times were subsecond for onset but more than a minute for recovery. The response required the chemotaxis signal protein CheY and receptor-dependent activation of its kinase CheA. The study of deletion mutants revealed a specific requirement for either the aerotaxis receptor Aer or the chemoreceptor Tar but not the Tar homolog Tsr. The action spectrum of the wild-type response was consistent with a flavin, but the chromophores remain to be identified. The motile response processed via Aer was sustained, with recovery to either step-up or -down taking more than a minute. The response processed via Tar was transient, recovering on second time scales comparable to chemotactic responses. The response duration and amplitude were dependent on relative expression of Aer, Tar, and Tsr. The main response features were reproduced when each receptor was expressed singly from a plasmid in a receptorless host strain. However, time-resolved motion analysis revealed subtle kinetic differences that reflect the role of receptor cluster interactions in kinase activation-deactivation dynamics.

Bacterial Proteins↗
PubMed1988

Aspartate taxis mutants of the Escherichia coli tar chemoreceptor.

The Tar protein of Escherichia coli belongs to a family of methyl-accepting inner membrane proteins that mediate chemotactic responses to a variety of compounds. These transmembrane signalers monitor the chemical environment by means of specific ligand-binding sites arrayed on the periplasmic side of the membrane, and in turn control cytoplasmic signals that modulate the flagellar rotational machinery. The periplasmic receptor domain of Tar senses two quite different chemoeffectors, aspartate and maltose. Aspartate is detected through direct binding to Tar molecules, whereas maltose is detected indirectly when complexed with the periplasmic maltose-binding protein. Saturating levels of either aspartate or maltose do not block behavioral responses to the other compound, indicating that the detection sites for these two attractants are not identical. We initiated structure-function studies of these chemoreceptor sites by isolating tar mutants which eliminate aspartate or maltose taxis, while retaining the ability to respond to the other chemoeffector. Mutants with greatly reduced aspartate taxis are described and characterized in this report. When present in single copy in the chromosome, these tar mutations generally eliminated chemotactic responses to aspartate and structurally related compounds, such as glutamate and methionine. Residual responses to these compounds were shifted to higher concentrations, indicating a reduced affinity of the aspartate-binding site in the mutant receptors. Maltose responses in the mutants ranged from 10 to 80% of normal, but had no detectable threshold shifts, indicating that these receptor alterations may have little effect on maltose detection sensitivity. The mutational changes in 17 mutants were determined by DNA sequence analysis. Each mutant exhibited a single amino acid replacement at residue 64, 69, or 73 in the Tar molecule. The wild-type Tar transducer contains arginines at all three of these positions, implying that electrostatic forces may play an important role in aspartate detection.

Aspartic Acid↗
PubMed1988

Purification and characterization of the wild-type and mutant carboxy-terminal domains of the Escherichia coli Tar chemoreceptor.

The carboxy-terminal half of the Escherichia coli Tar chemoreceptor protein was cloned into an overproducing plasmid with the transcription of the insert under the control of the strong hybrid tac promoter. Two dominant mutations in the tar gene, which result in "tumble-only" (tar-526) or "swim-only" (tar-529) phenotypes and which are postulated to produce proteins locked in specific signalling modes, were introduced separately onto the overproducing plasmid. After induction with isopropyl-beta-D-thiogalactopyranoside, cells containing the plasmids produced about 10% of their soluble cellular protein as the carboxy-terminal fragments. A scheme to purify the overproduced fragments was developed. Typical yields of pure fragment were 5, 30, and 20 mg per liter of induced culture for the wild type, 526 mutant, and 529 mutant, respectively. Fast-protein liquid chromatography-gel filtration analysis of the pure fragments showed that they all existed as oligomers (ca. 103,000 daltons), possibly trimers or tetramers (monomer size is 31,000 daltons). However, the 529 mutant fragment showed an additional oligomeric form (240,000 daltons) corresponding approximately to an octamer. When chromatographed in the presence of 1% octylglucoside, all three fragments showed an identical single oligomeric size of about 135,000 daltons. Further differences between the fragments such as ion-exchange behavior and susceptibility to degradation were found. Taken together, these results suggest that conformational differences between the 529 mutant fragment and the other fragments exist and that these differences may correlate with the phenotypic effects of the tar-529 mutation.

Bacterial Proteins↗
PubMed1997

Thermosensing properties of mutant aspartate chemoreceptors with methyl-accepting sites replaced singly or multiply by alanine.

The aspartate chemoreceptor Tar has a thermosensing function that is modulated by covalent modification of its four methylation sites (Gln295, Glu302, Gln309, and Glu491). Without posttranslational deamidation, Tar has no thermosensing ability. When Gln295 and Gln309 are deamidated to Glu, the unmethylated and heavily methylated forms function as warm and cold sensors, respectively. In this study, we carried out alanine-scanning mutagenesis of the methylation sites. Although alanine substitutions influenced the signaling bias and the methylation level, all of the mutants retained aspartate-sensing function. Those with single substitutions had almost normal thermosensing properties, indicating that substitutions at any particular methylation site do not seriously impair thermosensing function. In the posttranslational modification-defective background, some of the alanine substitutions restored thermosensing ability. Warm sensors were found among mutants retaining two glutamate residues, and cold sensors were found among those with one or no glutamate residue. This result suggests that the negative charge at the methylation sites is one factor that determines thermosensor phenotypes, although the size and shape of the side chain may also be important. The warm, cold, and null thermosensor phenotypes were clearly differentiated, and no intermediate phenotypes were found. Thus, the different thermosensing phenotypes that result from covalent modification of the methylation sites may reflect distinct structural states. Broader implications for the thermosensing mechanism are also discussed.

Alanine↗
PubMed1997

High- and low-abundance chemoreceptors in Escherichia coli: differential activities associated with closely related cytoplasmic domains.

In Escherichia coli, two high-abundance chemoreceptors are present in cellular dosages approximately ten-fold greater than two low-abundance receptors. In the absence of high-abundance receptors, cells exhibit an abnormally low tumble frequency and the ability of the remaining receptors to mediate directed migration in spatial gradients is substantially compromised. We found that increasing the cellular amount of the low-abundance receptor Trg over a range of dosages did not alleviate these defects and thus concluded that high- and low-abundance receptors are distinguished not simply by their different dosages in a wild-type cell but also by an inherent difference in activity. By creating hybrids of the low-abundance receptor Trg and the high-abundance receptor Tsr, we investigated the possibility that this inherent difference could be localized to a specific receptor domain and found that the cytoplasmic domain of the high-abundance receptor Tsr conferred the essential features of that receptor class on the low-abundance receptor Trg, even though it is in this domain that residue identity between the two receptors is substantially conserved.

Bacterial Proteins↗
PubMed1998

Chimeric chemoreceptors in Escherichia coli: signaling properties of Tar-Tap and Tap-Tar hybrids.

The Tap (taxis toward peptides) receptor and the periplasmic dipeptide-binding protein (DBP) of Escherichia coli together mediate chemotactic responses to dipeptides. Tap is a low-abundance receptor. It is present in 5- to 10-fold-fewer copies than high-abundance receptors like Tar and Tsr. Cells expressing Tap as the sole receptor, even from a multicopy plasmid at 5- to 10-fold-overexpressed levels, do not generate sufficient clockwise (CW) signal to tumble and thus swim exclusively smoothly (run). To study the signaling properties of Tap in detail, we constructed reciprocal hybrids between Tap and Tar fused in the linker region between the periplasmic and cytoplasmic domains. The Tapr hybrid senses dipeptides and is a good CW-signal generator, whereas the Tarp hybrid senses aspartate but is a poor CW-signal generator. Thus, the poor CW signaling of Tap is a property of its cytoplasmic domain. Eighteen residues at the carboxyl terminus of high-abundance receptors, including the NWETF sequence that binds the CheR methylesterase, are missing in Tap. The Tart protein, created by removing these 18 residues from Tar, has diminished CW-signaling ability. The Tapl protein, made by adding the last 18 residues of Tar to the carboxyl terminus of Tap, also does not support CW flagellar rotation. However, Tart and Tapl cross-react well with antibody directed against the conserved cytoplasmic region of Tsr, whereas Tap does not cross-react with this antibody. Tap does cross-react, however, with antibody directed against the low-abundance chemoreceptor Trg. The hybrid, truncated, and extended receptors exhibit various levels of methylation. However, Tar and Tapl, which contain a consensus CheR-binding motif (NWETF) at their carboxyl termini, exhibit the highest basal levels of methylation, as expected. We conclude that no simple correlation exists between the abundance of a receptor, its methylation level, and its CW-signaling ability.

Bacterial Proteins↗
PubMed2003

CheZ phosphatase localizes to chemoreceptor patches via CheA-short.

We have investigated the conditions required for polar localization of the CheZ phosphatase by using a CheZ-green fluorescent protein fusion protein that, when expressed from a single gene in the chromosome, restored chemotaxis to a DeltacheZ strain. Localization was observed in wild-type, DeltacheZ, DeltacheYZ, and DeltacheRB cells but not in cells with cheA, cheW, or all chemoreceptor genes except aer deleted. Cells making only CheA-short (CheA(S)) or CheA lacking the P2 domain also retained normal localization, whereas cells producing only CheA-long or CheA missing the P1 and P2 domains did not. We conclude that CheZ localization requires the truncated C-terminal portion of the P1 domain present in CheA(S). Missense mutations targeting residues 83 through 120 of CheZ also abolished localization. Two of these mutations do not disrupt chemotaxis, indicating that they specifically prevent interaction with CheA(S) while leaving other activities of CheZ intact.

Amino Acid Sequence↗
PubMed2006

Mutational analysis of the chemoreceptor-coupling domain of the Escherichia coli chemotaxis signaling kinase CheA.

During chemotactic signaling by Escherichia coli, autophosphorylation of the histidine kinase CheA is coupled to chemoreceptor control by the CheW protein, which interacts with the C-terminal P5 domain of CheA. To identify P5 determinants important for CheW binding and receptor coupling control, we isolated and characterized a series of P5 missense mutants. The mutants fell into four phenotypic groups on the basis of in vivo behavioral and protein stability tests and in vitro assays with purified mutant proteins. Group 1 mutants exhibited autophosphorylation and receptor-coupling defects, and their CheA proteins were subject to relatively rapid degradation in vivo. Group 1 mutations were located at hydrophobic residues in P5 subdomain 2 and most likely caused folding defects. Group 2 mutants made stable CheA proteins with normal autophosphorylation ability but with defects in CheW binding and in receptor-mediated activation of CheA autophosphorylation. Their mutations affected residues in P5 subdomain 1 near the interface with the CheA dimerization (P3) and ATP-binding (P4) domains. Mutant proteins of group 3 were normal in all tests yet could not support chemotaxis, suggesting that P5 has one or more important but still unknown signaling functions. Group 4 mutant proteins were specifically defective in receptor-mediated deactivation control. The group 4 mutations were located in P5 subdomain 1 at the P3/P3' interface. We conclude that P5 subdomain 1 is important for CheW binding and for receptor coupling control and that these processes may require substantial motions of the P5 domain relative to the neighboring P3 and P4 domains of CheA.

Bacterial Proteins↗
PubMed2004

Delayed chemoreceptor responses in infants with apnoea.

AIMS: To test the hypothesis that apnoea of infancy (AOI) is due to a deficit in chemoreception. METHODS: Tests were performed on 112 infants: 43 healthy control infants, 28 infants with periodic breathing or central apnoea (PBCA), and 41 infants with obstructive apnoea (OA) on overnight polysomnography. Chemoreceptor responses to hypercapnia (4% and 6% CO2 in air) for 6-8 minutes and hyperoxia (100% O2) for 60 seconds were expressed in terms of response strength and reaction time. Age at birth (gestational week 37-41) and age at test (2-34 postnatal weeks) were comparable across groups (median, min-max value). A total of 70 CO2 and 71 O2 tests were analysed. RESULTS: The strongest and fastest CO2 responders were control infants: their median increase in ventilation was 291%/kPaCO2 and their reaction time 16 breaths. In infants with PBCA and OA, the increase in ventilation was 41% and 130%/kPaCO2, and reaction time 64 and 54 breaths, respectively. There was a significant negative correlation between CO2 response strength and response time. In response to hyperoxia there was a comparable decrease in ventilation in all infants (12-20%), but a significantly longer response time in infants with apnoea (20 v 12 breaths). There was no correlation between the response strength and response time to O2 and CO2. CONCLUSION: An inappropriate central control of respiration is an important mechanism in the pathogenesis of apnoea of infancy.

Apnea↗
PubMed1987

Postnatal sensitivity of the peripheral chemoreceptors in newborn infants.

The peripheral chemoreflex was tested in healthy term infants by measuring the ventilatory response to 100% oxygen over 30 seconds. Minute ventilation did not change when studied two to six hours after birth. By contrast, at 2-6 days of age a mean decrease of 9.8% was noted, the difference between the groups being highly significant. There were no significant changes in respiratory rate. It is concluded that the chemoreflex is less active immediately after birth than it is a few days later, possibly due to a resetting of the sensitivity of the peripheral chemoreceptors from the fetal state, with its relatively low arterial oxygen tension to the higher postnatal concentrations.

Chemoreceptor Cells↗
PubMed2002

Peripheral chemoreceptor contributions to sympathetic and cardiovascular responses during hypercapnia.

We tested the hypothesis that integrated sympathetic and cardiovascular reflexes are modulated by systemic CO2 differently in hypoxia than in hyperoxia (n = 7). Subjects performed a CO2 rebreathe protocol that equilibrates CO2 partial pressures between arterial and venous blood and that elevates end tidal CO2 (PET(CO2)) from approximately 40 to approximately 58 mmHg. This test was repeated under conditions where end tidal oxygen levels were clamped at 50 (hypoxia) or 200 (hyperoxia) mmHg. Heart rate (HR; EKG), stroke volume (SV; Doppler ultrasound), blood pressure (MAP; finger plethysmograph), and muscle sympathetic nerve activity (MSNA) were measured continuously during the two protocols. MAP at 40 mmHg PET(CO2) (i.e., the first minute of the rebreathe) was greater during hypoxia versus hyperoxia (P < 0.05). However, the increase in MAP during the rebreathe (P < 0.05) was similar in hypoxia (16 +/- 3 mmHg) and hyperoxia (17 +/- 2 mmHg PET(CO2)). The increase in cardiac output (Q) at 55 mmHg PET(CO2) was greater in hypoxia (2.61 +/- 0.7 L/min) versus hyperoxia (1.09 +/- 0.44 L/min) (P < 0.05). In both conditions the increase in Q was due to elevations in both HR and SV (P < 0.05). Systemic vascular conductance (SVC) increased to similar absolute levels in both conditions but rose earlier during hypoxia (> 50 mmHg PET(CO2)) than hyperoxia (> 55 mmHg). MSNA increased earlier during hypoxic hypercapnia (> 45 mmHg) compared with hyperoxic hypercapnia (> 55 mmHg). Thus, in these conscious humans, the dose-response effect of PET(CO2) on the integrated cardiovascular responses was shifted to the left during hypoxic hypercapnia. The combined data indicate that peripheral chemoreceptors exert important influence over cardiovascular reflex responses to hypercapnia.

Adrenergic Fibers↗
PubMed1981

Carotid chemoreceptors and vagi in hypoxic and cyanide-induced tachycardia in the dog.

We investigated the mechanisms underlying heart rate changes resulting from systemic hypoxia in anesthetized artificially ventilated dogs with low control heart rate (less than or equal to 93 beats/min). We observed that systemic hypoxia evoked tachycardia in intact dogs that was not significantly different from that evoked in dogs with beta-adrenergic blockade (BB). Also, tachycardia elicited in dogs with BB plus spinal section at C3 (BBSS) was significantly greater than in dogs with BBSS plus bilateral section of carotid sinus nerves. Furthermore, under various anesthetics, intracarotid injection of sodium cyanide induced a tachycardia response in dogs with low control heart rate (less than or equal to 97 beats/min) and a bradycardia response in dogs with high control heart rate (greater than or equal to 130 beats/min). These results suggest that 1) when the resting cardiac parasympathetic tone is high, systemic hypoxia evokes tachycardia which is mediated predominantly through efferent vagus nerves and 2) the stimulation of carotid chemoreceptors causes excitation of both cardioacceleratory and cardioinhibitory reflexes, the resultant response being dependent on the prevalent autonomic drive.

Animals↗