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Transmembrane signal transduction by cofactor transport.

ABSTRACT: Information processing and cell signalling in biological systems relies on passing chemical signals across lipid bilayer membranes, but examples of synthetic systems that can achieve this process are rare. A synthetic transducer has been developed that triggers catalytic hydrolysis of an ester substrate inside lipid vesicles in response to addition of metal ions to the external vesicle solution. The output signal generated in the internal compartment of the vesicles is produced by binding of a metal ion cofactor to a head group on the transducer to form a catalytically competent complex. The mechanism of signal transduction is based on transport of the metal ion cofactor across the bilayer by the transducer, and the system can be reversibly switched between on and off states by adding cadmium(ii) and ethylene diamine tetracarboxylic acid input signals respectively. The transducer is also equipped with a hydrazide moiety, which allows modulation of activity through covalent conjugation with aldehydes. Conjugation with a sugar derivative abolished activity, because the resulting hydrazone is too polar to cross the bilayer, whereas conjugation with a pyridine derivative increased activity. Coupling transport with catalysis provides a straightforward mechanism for generating complex systems using simple components.

SUBMITTER: Kocsis I

PROVIDER: S-EPMC8480319 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Artificial transmembrane signal transduction mediated by dynamic covalent chemistry.

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| S-EPMC8565364 | biostudies-literature

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Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors.

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Project description:To determine whether N-terminal sequences are involved in the transmembrane signaling mechanism of EnvZ, the nucleotide sequences of envZ genes from several enteric bacteria were determined. Comparative analysis revealed that the amino acid sequence between Pro41 and Glu53 was highly conserved. To further analyze the role of the conserved sequence, envZ of Escherichia coli was subjected to random PCR mutagenesis and mutant alleles that produced a high-osmolarity phenotype, in which ompF was repressed, were isolated. The mutations identified clustered within, as well as adjacent to, the Pro41-to-Glu53 sequence. These findings suggest that the conserved Pro41-to-Glu53 sequence is involved in the signal transduction mechanism of EnvZ.

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Common extracellular sensory domains in transmembrane receptors for diverse signal transduction pathways in bacteria and archaea.

Project description:Transmembrane receptors in microorganisms, such as sensory histidine kinases and methyl-accepting chemotaxis proteins, are molecular devices for monitoring environmental changes. We report here that sensory domain sharing is widespread among different classes of transmembrane receptors. We have identified two novel conserved extracellular sensory domains, named CHASE2 and CHASE3, that are found in at least four classes of transmembrane receptors: histidine kinases, adenylate cyclases, predicted diguanylate cyclases, and either serine/threonine protein kinases (CHASE2) or methyl-accepting chemotaxis proteins (CHASE3). Three other extracellular sensory domains were shared by at least two different classes of transmembrane receptors: histidine kinases and either diguanylate cyclases, adenylate cyclases, or phosphodiesterases. These observations suggest that microorganisms use similar conserved domains to sense similar environmental signals and transmit this information via different signal transduction pathways to different regulatory circuits: transcriptional regulation (histidine kinases), chemotaxis (methyl-accepting proteins), catabolite repression (adenylate cyclases), and modulation of enzyme activity (diguanylate cyclases and phosphodiesterases). The variety of signaling pathways using the CHASE-type domains indicates that these domains sense some critically important extracellular signals.

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Ras/cAMP signal transduction, perturbations

Project description:Disruption of Ras/cAMP signaling by perturbation of pathway elements and controlled cAMP concentration. All cultures grown in SC medium. Keywords: other

2005-10-01 | GSE2927 | GEO

THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.

Project description:Characterization of previously described intraflagellar transport (IFT) mouse mutants has led to the proposition that normal primary cilia are required for mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe an N-ethyl-N-nitrosourea-induced mutant mouse, alien (aln), which has abnormal primary cilia and shows overactivation of the SHH pathway. The aln locus encodes a novel protein, THM1 (tetratricopeptide repeat-containing hedgehog modulator-1), which localizes to cilia. aln-mutant cilia have bulb-like structures at their tips in which IFT proteins (such as IFT88) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA-interference knockdown of Ttc21b (which we call Thm1 and which encodes THM1) in mouse inner medullary collecting duct cells expressing an IFT88-enhanced yellow fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and live imaging of these cells revealed impaired retrograde IFT. In contrast to previously described IFT mutants, Smoothened and full-length glioblastoma (GLI) proteins localize to aln-mutant cilia. We hypothesize that the aln retrograde IFT defect causes sequestration of IFT proteins in aln-mutant cilia and leads to the overactivated SHH signaling phenotype. Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in SHH signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event.

| S-EPMC4817720 | biostudies-literature

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