Integration of signal-transduction processes

1988 ◽  
Vol 66 (6) ◽  
pp. 557-566 ◽  
Author(s):  
Marilyn J. Mooibroek ◽  
Jerry H. Wang

The adenylate cyclase – cAMP, phospholipase C – IP3 (inositol 1,4,5-triphosphate), and DAG (diacylglycerol) signal transduction systems are used to illustrate general principles underlying the process of information transfer during cell stimulation. Both systems consist of reaction cascades that convert the external signal to an intracellular messenger, translate the messenger to regulatory activities, and then modulate the activities of appropriate cellular proteins to result in specific cell responses. Almost all of these reactions are under second-messenger-dependent regulation, with many being regulated by multiple messengers. Such complex regulation provides ample opportunities for the fine-tuning of the signal cascades and for coordination between cascades during cell stimulation. Specific examples are used to illustrate how the cell uses different intrasystem and intersystem regulatory reactions to achieve specific responses.

2021 ◽  
Vol 383 (1) ◽  
pp. 113-123
Author(s):  
Sudeshna Das Chakraborty ◽  
Silke Sachse

AbstractSensing olfactory signals in the environment represents a crucial and significant task of sensory systems in almost all organisms to facilitate survival and reproduction. Notably, the olfactory system of diverse animal phyla shares astonishingly many fundamental principles with regard to anatomical and functional properties. Binding of odor ligands by chemosensory receptors present in the olfactory peripheral organs leads to a neuronal activity that is conveyed to first and higher-order brain centers leading to a subsequent odor-guided behavioral decision. One of the key centers for integrating and processing innate olfactory behavior is the lateral horn (LH) of the protocerebrum in insects. In recent years the LH of Drosophila has garnered increasing attention and many studies have been dedicated to elucidate its circuitry. In this review we will summarize the recent advances in mapping and characterizing LH-specific cell types, their functional properties with respect to odor tuning, their neurotransmitter profiles, their connectivity to pre-synaptic and post-synaptic partner neurons as well as their impact for olfactory behavior as known so far.


2018 ◽  
Vol 92 (8) ◽  
pp. e02133-17 ◽  
Author(s):  
Danushka K. Wijesundara ◽  
Jason Gummow ◽  
Yanrui Li ◽  
Wenbo Yu ◽  
Benjamin J. Quah ◽  
...  

ABSTRACTA universal hepatitis C virus (HCV) vaccine should elicit multiantigenic, multigenotypic responses, which are more likely to protect against challenge with the range of genotypes and subtypes circulating in the community. A vaccine cocktail and vaccines encoding consensus HCV sequences are attractive approaches to achieve this goal. Consequently, in a series of mouse vaccination studies, we compared the immunogenicity of a DNA vaccine encoding a consensus HCV nonstructural 5B (NS5B) protein to that of a cocktail of DNA plasmids encoding the genotype 1b (Gt1b) and Gt3a NS5B proteins. To complement this study, we assessed responses to a multiantigenic cocktail regimen by comparing a DNA vaccine cocktail encoding Gt1b and Gt3a NS3, NS4, and NS5B proteins to a single-genotype NS3/4/5B DNA vaccine. To thoroughly evaluatein vivocytotoxic T lymphocyte (CTL) and T helper (Th) cell responses against Gt1b and Gt3a HCV peptide-pulsed target cells, we exploited a novel fluorescent-target array (FTA). FTA and enzyme-linked immunosorbent spot (ELISpot) analyses collectively indicated that the cocktail regimens elicited higher responses to Gt1b and Gt3a NS5B proteins than those with the consensus vaccine, while the multiantigenic DNA cocktail significantly increased the responses to NS3 and NS5B compared to those elicited by the single-genotype vaccines. Thus, a DNA cocktail vaccination regimen is more effective than a consensus vaccine or a monovalent vaccine at increasing the breadth of multigenotypic T cell responses, which has implications for the development of vaccines for communities where multiple HCV genotypes circulate.IMPORTANCEDespite the development of highly effective direct-acting antivirals (DAA), infections with hepatitis C virus (HCV) continue, particularly in countries where the supply of DAA is limited. Furthermore, patients who eliminate the virus as a result of DAA therapy can still be reinfected. Thus, a vaccine for HCV is urgently required, but the heterogeneity of HCV strains makes the development of a universal vaccine difficult. To address this, we developed a novel cytolytic DNA vaccine which elicits robust cell-mediated immunity (CMI) to the nonstructural (NS) proteins in vaccinated animals. We compared the immune responses against genotypes 1 and 3 that were elicited by a consensus DNA vaccine or a DNA vaccine cocktail and showed that the cocktail induced higher levels of CMI to the NS proteins of both genotypes. This study suggests that a universal HCV vaccine can most readily be achieved by use of a DNA vaccine cocktail.


2019 ◽  
Vol 128 (06/07) ◽  
pp. 395-400 ◽  
Author(s):  
Heike Biebermann ◽  
Gunnar Kleinau

AbstractThe thyroid hormone metabolite 3-iodothyronamine (3-T1AM) exerts diverse physiological reactions such as a decrease of body temperature, and negative inotropic and chronotropic effects. This observed pleomorphic effect in physiology can be barely explained by interaction with only one target protein such as the trace-amine receptor 1 (TAAR1), a class A G-protein coupled receptor (GPCR). Moreover, Taar1 knock-out mice still react to 3-T1AM through physiological responses with a rapid decrease in body temperature. These facts propelled our group and others to search for further targets for this molecule.The group of TAARs evolved early in evolution and, according to sequence similarities, they are closely related to adrenoceptors and other aminergic receptors. Therefore, several of these receptors were characterized by their potential to interplay with 3-T1AM. Indeed, 3-T1AM acts as a positive allosteric modulator on the beta2-adrenoceptor (ADRB2) and as a biased agonist on the serotonin receptor 1B (5HT1b) and the alpha2-adrenoceptor (ADRA2A). In addition, 3-T1AM was reported to be a weak antagonist at a non-aminergic muscarinic receptor (M3).These findings impressively reflect that such trace amines can unselectively and simultaneously function at different receptors expressed by one cell or at different tissues. In conclusion, the role of 3-T1AM is hypothesized to concert the fine-tuning of specific cell reactions by the accentuation of certain pathways dependent on distinct receptors. 3-T1AM acts as a regulator of signals by blocking, modulating, or inducing simultaneously distinct intracellular signaling cascades via different GPCRs.


2020 ◽  
Vol 6 (51) ◽  
pp. eabd3590
Author(s):  
Yongkun Ji ◽  
Xingan Li ◽  
Ting Ji ◽  
Junbo Tang ◽  
Lifei Qiu ◽  
...  

Animals with recent shared ancestry frequently adapt in parallel to new but similar habitats, a process often underlined by repeated selection of the same genes. Yet, in contrast, few examples have demonstrated the significance of gene reuse in colonization of multiple disparate habitats. By analyzing 343 genomes of the widespread Asian honeybee, Apis cerana, we showed that multiple peripheral subspecies radiated from a central ancestral population and adapted independently to diverse habitats. We found strong evidence of gene reuse in the Leucokinin receptor (Lkr), which was repeatedly selected in almost all peripheral subspecies. Differential expression and RNA interference knockdown revealed the role of Lkr in influencing foraging labor division, suggesting that Lkr facilitates collective tendency for pollen/nectar collection as an adaptation to floral changes. Our results suggest that honeybees may accommodate diverse floral shifts during rapid radiation through fine-tuning individual foraging tendency, a seemingly complex process accomplished by gene reuse.


Author(s):  
M. D. MADULARA ◽  
P. A. B. FRANCISCO ◽  
S. NAWANG ◽  
D. C. AROGANCIA ◽  
C. J. CELLUCCI ◽  
...  

We investigate the pairwise mutual information and transfer entropy of ten-channel, free-running electroencephalographs measured from thirteen subjects under two behavioral conditions: eyes open resting and eyes closed resting. Mutual information measures nonlinear correlations; transfer entropy determines the directionality of information transfer. For all channel pairs, mutual information is generally lower with eyes open compared to eyes closed indicating that EEG signals at different scalp sites become more dissimilar as the visual system is engaged. On the other hand, transfer entropy increases on average by almost two-fold when the eyes are opened. The largest one-way transfer entropies are to and from the Oz site consistent with the involvement of the occipital lobe in vision. The largest net transfer entropies are from F3 and F4 to almost all the other scalp sites.


2019 ◽  
Vol 20 (11) ◽  
pp. 2668 ◽  
Author(s):  
Hsueh-Fen Chen ◽  
Huai-Chia Chuang ◽  
Tse-Hua Tan

Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or spatiotemporal profiles of MAPK activities. Hence, DUSPs need to be properly controlled. Protein post-translational modifications, such as ubiquitination, phosphorylation, methylation, and acetylation, play important roles in the regulation of protein stability and activity. Ubiquitination is critical for controlling protein degradation, activation, and interaction. For DUSPs, ubiquitination induces degradation of eight DUSPs, namely, DUSP1, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, and DUSP16. In addition, protein stability of DUSP2 and DUSP10 is enhanced by phosphorylation. Methylation-induced ubiquitination of DUSP14 stimulates its phosphatase activity. In this review, we summarize the knowledge of the regulation of DUSP stability and ubiquitination through post-translational modifications.


2005 ◽  
Vol 6 (10) ◽  
pp. 961-962 ◽  
Author(s):  
Marco Colonna
Keyword(s):  
Nk Cell ◽  

2017 ◽  
Vol 114 (6) ◽  
pp. 1401-1406 ◽  
Author(s):  
Ronan Chéreau ◽  
G. Ezequiel Saraceno ◽  
Julie Angibaud ◽  
Daniel Cattaert ◽  
U. Valentin Nägerl

Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.


2009 ◽  
Vol 02 (01) ◽  
pp. 93-100 ◽  
Author(s):  
LING ZHU ◽  
TIMON CHENG-YI LIU ◽  
MIN WU ◽  
JIAN-QIN YUAN ◽  
TONG-SHENG CHEN

Photobiomodulation (PBM) is a modulation of monochromatic light or laser irradiation (LI) on biosystems. It is reviewed from the viewpoint of extraocular phototransduction in this paper. It was found that LI can induce extraocular phototransduction, and there may be an exact correspondence relationship of LI at different wavelengths and in different dose zones, and cellular signal transduction pathways. The signal transduction pathways can be classified into two types so that the Gs protein-mediated pathways belong to pathway 1, and the other pathways such as protein kinase Cs -mediated pathways and mitogen-activated protein kinase-mediated pathways belong to pathway 2. Almost all the present pathways found to mediate PBM belong to pathway 2, but there should be a pathway 1-mediated PBM. The previous studies were rather preliminary, and therefore further work should be done.


1992 ◽  
Vol 3 (9) ◽  
pp. 981-987 ◽  
Author(s):  
T Hultsch ◽  
R Martin ◽  
R J Hohman

The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of activities with respect to IgE receptor (Fc epsilon RI)-mediated exocytosis from mast cells and T cell receptor-mediated transcription of IL-2. These findings suggest a common step in receptor-mediated signal transduction leading to exocytosis and transcription and imply that immunosuppressive drugs target specific signal transduction pathways, rather than specific cell types. This hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is prevented in a competitive manner by FK506, a structural analogue of rapamycin. Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also inhibited, at doses comparable to those shown previously to inhibit IL-2-dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast, proliferation of A-431 cells, a epidermoid cell line, was not affected by rapamycin. DNA histograms indicate that complexes formed between the rapamycin-FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit proliferative signals emanating from IL-3 receptors, resulting in growth arrest of cytokine-dependent, hematopoietic cells.


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