scholarly journals Conceptual Evolution of Cell Signaling

2019 ◽  
Vol 20 (13) ◽  
pp. 3292 ◽  
Author(s):  
Arathi Nair ◽  
Prashant Chauhan ◽  
Bhaskar Saha ◽  
Katharina F. Kubatzky

During the last 100 years, cell signaling has evolved into a common mechanism for most physiological processes across systems. Although the majority of cell signaling principles were initially derived from hormonal studies, its exponential growth has been supported by interdisciplinary inputs, e.g., from physics, chemistry, mathematics, statistics, and computational fields. As a result, cell signaling has grown out of scope for any general review. Here, we review how the messages are transferred from the first messenger (the ligand) to the receptor, and then decoded with the help of cascades of second messengers (kinases, phosphatases, GTPases, ions, and small molecules such as cAMP, cGMP, diacylglycerol, etc.). The message is thus relayed from the membrane to the nucleus where gene expression ns, subsequent translations, and protein targeting to the cell membrane and other organelles are triggered. Although there are limited numbers of intracellular messengers, the specificity of the response profiles to the ligands is generated by the involvement of a combination of selected intracellular signaling intermediates. Other crucial parameters in cell signaling are its directionality and distribution of signaling strengths in different pathways that may crosstalk to adjust the amplitude and quality of the final effector output. Finally, we have reflected upon its possible developments during the coming years.

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Gerald Thiel ◽  
Tobias Schmidt ◽  
Oliver G. Rössler

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Brendon Ford ◽  
Mark Halaki ◽  
Joanna Diong ◽  
Karen A Ginn

AbstractObjectivesExperimental pain is a commonly used method to draw conclusions about the motor response to clinical musculoskeletal pain. A systematic review was performed to determine if current models of acute experimental pain validly replicate the clinical experience of appendicular musculoskeletal pain with respect to the distribution and quality of pain and the pain response to provocation testing.MethodsA structured search of Medline, Scopus and Embase databases was conducted from database inception to August 2020 using the following key terms: “experimental muscle pain” OR “experimental pain” OR “pain induced” OR “induced pain” OR “muscle hyperalgesia“ OR (“Pain model” AND “muscle”). Studies in English were included if investigators induced experimental musculoskeletal pain into a limb (including the sacroiliac joint) in humans, and if they measured and reported the distribution of pain, quality of pain or response to a provocation manoeuvre performed passively or actively. Studies were excluded if they involved prolonged or delayed experimental pain, if temporomandibular, orofacial, lumbar, thoracic or cervical spine pain were investigated, if a full text of the study was not available or if they were systematic reviews. Two investigators independently screened each title and abstract and each full text paper to determine inclusion in the review. Disagreements were resolved by consensus with a third investigator.ResultsData from 57 experimental pain studies were included in this review. Forty-six of these studies reported pain distribution, 41 reported pain quality and six detailed the pain response to provocation testing. Hypertonic saline injection was the most common mechanism used to induce pain with 43 studies employing this method. The next most common methods were capsaicin injection (5 studies) and electrical stimulation, injection of acidic solution and ischaemia with three studies each. The distribution of experimental pain was similar to the area of pain reported in clinical appendicular musculoskeletal conditions. The quality of appendicular musculoskeletal pain was not replicated with the affective component of the McGill Pain Questionnaire consistently lower than that typically reported by musculoskeletal pain patients. The response to provocation testing was rarely investigated following experimental pain induction. Based on the limited available data, the increase in pain experienced in clinical populations during provocative maneuvers was not consistently replicated.ConclusionsCurrent acute experimental pain models replicate the distribution but not the quality of chronic clinical appendicular musculoskeletal pain. Limited evidence also indicates that experimentally induced acute pain does not consistently increase with tests known to provoke pain in patients with appendicular musculoskeletal pain. The results of this review question the validity of conclusions drawn from acute experimental pain studies regarding changes in muscle behaviour in response to pain in the clinical setting.


Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 397 ◽  
Author(s):  
Anket Sharma ◽  
Bingsong Zheng

Plant grafting is an important horticulture technique used to produce a new plant after joining rootstock and scion. This is one of the most used techniques by horticulturists to enhance the quality and production of various crops. Grafting helps in improving the health of plants, their yield, and the quality of plant products, along with the enhancement of their postharvest life. The main process responsible for successful production of grafted plants is the connection of vascular tissues. This step determines the success rate of grafts and hence needs to be studied in detail. There are many factors that regulate the connection of scion and stock, and plant hormones are of special interest for researchers in the recent times. These phytohormones act as signaling molecules and have the capability of translocation across the graft union. Plant hormones, mainly auxins, cytokinins, and gibberellins, play a major role in the regulation of various key physiological processes occurring at the grafting site. In the current review, we discuss the molecular mechanisms of graft development and the phytohormone-mediated regulation of the growth and development of graft union.


Vestnik ◽  
2021 ◽  
pp. 208-214
Author(s):  
Б.К. Кайрат ◽  
С.Т. Тулеуханов ◽  
В.П. Зинченко

Ионы Са являются основным мессенджером в регуляции физиологических функций клеток. Внутриклеточном пространстве ионы Ca могут свободно состоянии диффундироваться в различных частях цитоплазмы, в то же время значительное количество Ca в связанном виде накапливается в различных внутриклеточных депо или в составе кальций-связывающих белков. Регуляция физиологических процессов с ионами внутриклеточного Са происходит в диапазоне концентраций 10 М, тогда как концентрация Са во внеклеточном пространстве выше и составляет 10 М, для поддержании градиента концентраций в клетках имеются важные Са транспортирующие системы плазматической мембраны, эндоплазматического ретикулума и митохондрий. В нейронах функционируют внутриклеточные ферменты и белки плазматической мембраны для поддержания Са-гомеостаза и реализации механизмов внутриклеточной сигнализации для обеспечения жизнедеятельности в выживании клеток. Нарушение или гиперактивация одного или нескольких механизмов кальциевой сигнализации может привести к повреждению и гибели нейронов в случае отсутствия компенсаторных механизмов. Ca ions are a key messenger for the regulation of most of the physiological functions of cells. Inside the cell, Ca ions can freely diffuse in various parts of the cytoplasm, but a significant amount of Ca is also bound in various intracellular depots or in the form of calcium-binding proteins. The regulation of physiological processes by intracellular Ca ions occurs in the concentration range of 10 M, and the concentration of Ca in the extracellular space is higher and is 10 M, and to maintain this concentration gradient, cells have Ca-transporting systems of the plasma membrane, endoplasmic reticulum and mitochondria. In neurons, a large number of intracellular enzymes and plasma membrane proteins function to maintain Ca-homeostasis and implement intracellular signaling mechanisms to ensure vital activity in the survival of cells. Violation or hyperactivation of one or more mechanisms of calcium signaling can lead to cell damage and death in the absence of compensatory mechanisms.


2003 ◽  
Vol 1 (1) ◽  
pp. 25-32 ◽  
Author(s):  
G. Spoto ◽  
A. Contento ◽  
M. Di Nicola ◽  
G. Bianchi ◽  
C. Di Giulio ◽  
...  

Phosphodiesterase activity was tested on homogenized eyes of young and old rats kept in hypoxic and hyperoxic conditions, with the aim of correlating any difference in PDE activity with aging and variations in atmospheric oxygen contents. The activities of the two enzymes, cAMP phosphodiesterase (cAMP-PDE) and cGMP phosphodiesterase (cGMP-PDE), were tested. Phosphodiesterases seem to be particularly susceptible to variations in oxygen tension, suggesting an important role of cyclic nucleotides in cellular adaptive processes. Particularly, cAMP-PDE activity increases lightly both in hypoxic and hyperoxic conditions in young and old rats. For cGMP-PDE activity of young rats, a similar behaviour to cAMP-PDE activity is observed with a similar increase in hypoxic and hyperoxic conditions respect to the control rats. Instead old rats seem to be quite insensible to hypoxia, while they show a fair increase in cGMP-PDE activity in the case of hyperoxia. The second messengers cAMP and cGMP play important roles in mediating the biological effects of a wide variety of first messengers. The intracellular levels of cyclic nucleotides depend upon rates of synthesis and degradation, actuated, respectively, by cyclases and phosphodiesterases (PDEs). Therefore, PDEs seem to play an important role in a wide variety of physiological processes.


2012 ◽  
Vol 36 (2) ◽  
pp. 229-235 ◽  
Author(s):  
Renata Conduru Ribeiro Reis ◽  
Claudinéia Regina Pelacani ◽  
Cimille Gabrielle Cardoso Antunes ◽  
Bárbara França Dantas ◽  
Renato Delmondez de Castro

Studies of seed physiological processes represent the starting point for the sustainable utilization of native or cultivated plant species from the caatinga biome for which germination studies are still scarce. In order to determine adequate methods for the conservation of Gliricidia sepium seeds, the physiological quality of propagules exposed to different conditions and times of storage were examined. Recently collected seeds of G. sepium were analyzed immediately, while the other sample was stored for three, six, nine, or twelve months in plastic or paper bags under refrigeration or at room temperature for further analysis. The germination rates of seeds from each storage regime were determined and these rates compared to their water content. It was observed that germination capacity was directly related to changes in seed humidity. Storing seeds in plastic bags yielded the best conservation, mainly when they were stored at low temperatures. However, even at temperatures near 25°C it was possible to prolong seed viability when their water content was controlled through the use of impermeable packing.


2016 ◽  
Vol 4 (4) ◽  
pp. 28
Author(s):  
Sabri Braha ◽  
Petrit Rama

The purpose of this research is to determine the impact of the turf-only substrate and turf–perlite in the ratio 2:1 and of growth regulators in the quality of adventive roots ( the number and length) of well lignified one-year old branches without fruit buds in the Bluecrop cultivar (Vaccinium corymbosum L.) taken at the end of the latent period before budding at the February 15 th during the -2015 growing season. In order to support the increase of the number of roots and their length the hardwood cuttings are treated with different IBA and NAA concentrations (1500, 3000, 4500 ppm), while a part of cuttings were untreated control. The number and the length of roots have increased in relation to the increase of concentration from 1500 to 3000 ppm followed by a decline of these values in concentrations over 3000 ppm. Respectively, the number of roots (8) and the higher values of root length (4.6 cm) are achieved in the turf–perlite substrate, IBA 3000 ppm (compared to the turf-only substrate). The presence of perlite helps the aeration of the substrate and supports biochemical and physiological processes which lead to the inducing of adventive roots. Regarding the number and length of roots an important variation for (p<0.05) was observed between different concentrations of IBA and NAA. In general the effect of IBA was a lot better than the effect of NAA.


Author(s):  
Yuehui Tian ◽  
Shang Yang ◽  
Shiqiang Gao

Second messengers, cyclic adenosine 3'-5'-monophosphate (cAMP) and cyclic guanosine 3'-5'-monophosphate (cGMP) are playing important roles in many animal cells by regulating intracellular signaling pathways and modulating cell physiology. Environmental cues like temperature, light and chemical compounds can stimulate cell surface receptors and trigger the generation of second messengers and the following regulations. Spread of cAMP and cGMP is further shaped by cyclic nucleotide phosphodiesterases (PDEs) for orchestration of intracellular microdomain signaling. However, localized intracellular cAMP and cGMP signaling requires further investigation. Optogenetic manipulation of cAMP and cGMP offers new opportunities of spatio-temporally precise study of their signaling mechanism. Light-gated nucleotide cyclases are well developed and applied for cAMP/cGMP manipulation. Recently discovered rhodopsin phosphodiesterase gene from protists established new and direct biological connection between light and PDEs. Light-regulated PDEs are under development and of demand to complete the toolkit of cAMP/cGMP manipulation. In this review, we summarize the state of the art, pros and cons of artificial and natural light-regulated PDEs and discuss potential new strategies of developing light-gated PDEs for optogenetic manipulation.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Flurina Boehi ◽  
Patrick Manetsch ◽  
Michael O. Hottiger

AbstractSignaling cascades provide integrative and interactive frameworks that allow the cell to respond to signals from its environment and/or from within the cell itself. The dynamic regulation of mammalian cell signaling pathways is often modulated by cascades of protein post-translational modifications (PTMs). ADP-ribosylation is a PTM that is catalyzed by ADP-ribosyltransferases and manifests as mono- (MARylation) or poly- (PARylation) ADP-ribosylation depending on the addition of one or multiple ADP-ribose units to protein substrates. ADP-ribosylation has recently emerged as an important cell regulator that impacts a plethora of cellular processes, including many intracellular signaling events. Here, we provide an overview of the interplay between the intracellular diphtheria toxin-like ADP-ribosyltransferase (ARTD) family members and five selected signaling pathways (including NF-κB, JAK/STAT, Wnt-β-catenin, MAPK, PI3K/AKT), which are frequently described to control or to be controlled by ADP-ribosyltransferases and how these interactions impact the cellular responses.


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