Abstract:Eukaryotic chemoattraction signal transduction pathways, such as those used by Dictyostelium discoideum to move toward cAMP, use a G protein–coupled receptor to activate multiple conserved pathways such as PI3 kinase/Akt/PKB to induce actin polymerization and pseudopod formation at the front of a cell, and PTEN to localize myosin II to the rear of a cell. Relatively little is known about chemorepulsion. We previously found that AprA is a chemorepellent protein secreted by Dictyostelium cells. Here we used 29 c… Show more
“…C, an essential component of 8CPT-cAMP induced chemorepulsion, is not essential for AprA induced chemorepulsion (Keizer-Gunnink et al, 2007, Phillips and Gomer, 2012, Rijal et al, 2018. Together, these results suggest that chemoattraction and chemorepulsion use partially overlapping sets of signal transduction pathways.…”
Section: Fig 1 Chemoattraction and Chemorepulsion If A Single Cellmentioning
confidence: 85%
“…As with the chemoattractants cAMP and folic acid, AprA is sensed by a G protein coupled receptor called GrlH (Tang et al, 2018). As with chemoattraction to cAMP, AprA also induces Ras activation, and Ras activity is required for AprA-induced chemorepulsion (Rijal et al, 2018). AprA-induced chemorepulsion utilizes components of the TorC2, Phospholipase A, and MAP kinase pathways used for chemoattraction to cAMP, as well as the calcium channel component IplA and protein kinase C. Both phosphatase and tensin homolog (PTEN), which is involved in chemoattraction to cAMP, and the PTENlike protein CnrN are required for AprA induced chemorepulsion (Herlihy et al, 2013b, Rijal et al, 2018.…”
Section: Chemorepulsion Away From Apramentioning
confidence: 99%
“…As with chemoattraction to cAMP, AprA also induces Ras activation, and Ras activity is required for AprA-induced chemorepulsion (Rijal et al, 2018). AprA-induced chemorepulsion utilizes components of the TorC2, Phospholipase A, and MAP kinase pathways used for chemoattraction to cAMP, as well as the calcium channel component IplA and protein kinase C. Both phosphatase and tensin homolog (PTEN), which is involved in chemoattraction to cAMP, and the PTENlike protein CnrN are required for AprA induced chemorepulsion (Herlihy et al, 2013b, Rijal et al, 2018. However, chemorepulsion from AprA does not require other components of the cAMP signal transduction pathway such as guanylyl cyclase, El-moE, and the PI3K/ PIP3 pathways.…”
In the last few decades, we have learned a considerable amount about how eukaryotic cells communicate with each other, and what it is the cells are telling each other. The simplicity of Dictyostelium discoideum, and the wide variety of available tools to study this organism, makes it the equivalent of a hydrogen atom for cell and developmental biology. Studies using Dictyostelium have pioneered a good deal of our understanding of eukaryotic cell communication. In this review, we will present a brief overview of how Dictyostelium cells use extracellular signals to attract each other, repel each other, sense their local cell density, sense whether the nearby cells are starving or stressed, count themselves to organize the formation of structures containing a regulated number of cells, sense the volume they are in, and organize their multicellular development. Although we are probably just beginning to learn what the cells are telling each other, the elucidation of Dictyostelium extracellular signals has already led to the development of possible therapeutics for human diseases.
“…C, an essential component of 8CPT-cAMP induced chemorepulsion, is not essential for AprA induced chemorepulsion (Keizer-Gunnink et al, 2007, Phillips and Gomer, 2012, Rijal et al, 2018. Together, these results suggest that chemoattraction and chemorepulsion use partially overlapping sets of signal transduction pathways.…”
Section: Fig 1 Chemoattraction and Chemorepulsion If A Single Cellmentioning
confidence: 85%
“…As with the chemoattractants cAMP and folic acid, AprA is sensed by a G protein coupled receptor called GrlH (Tang et al, 2018). As with chemoattraction to cAMP, AprA also induces Ras activation, and Ras activity is required for AprA-induced chemorepulsion (Rijal et al, 2018). AprA-induced chemorepulsion utilizes components of the TorC2, Phospholipase A, and MAP kinase pathways used for chemoattraction to cAMP, as well as the calcium channel component IplA and protein kinase C. Both phosphatase and tensin homolog (PTEN), which is involved in chemoattraction to cAMP, and the PTENlike protein CnrN are required for AprA induced chemorepulsion (Herlihy et al, 2013b, Rijal et al, 2018.…”
Section: Chemorepulsion Away From Apramentioning
confidence: 99%
“…As with chemoattraction to cAMP, AprA also induces Ras activation, and Ras activity is required for AprA-induced chemorepulsion (Rijal et al, 2018). AprA-induced chemorepulsion utilizes components of the TorC2, Phospholipase A, and MAP kinase pathways used for chemoattraction to cAMP, as well as the calcium channel component IplA and protein kinase C. Both phosphatase and tensin homolog (PTEN), which is involved in chemoattraction to cAMP, and the PTENlike protein CnrN are required for AprA induced chemorepulsion (Herlihy et al, 2013b, Rijal et al, 2018. However, chemorepulsion from AprA does not require other components of the cAMP signal transduction pathway such as guanylyl cyclase, El-moE, and the PI3K/ PIP3 pathways.…”
In the last few decades, we have learned a considerable amount about how eukaryotic cells communicate with each other, and what it is the cells are telling each other. The simplicity of Dictyostelium discoideum, and the wide variety of available tools to study this organism, makes it the equivalent of a hydrogen atom for cell and developmental biology. Studies using Dictyostelium have pioneered a good deal of our understanding of eukaryotic cell communication. In this review, we will present a brief overview of how Dictyostelium cells use extracellular signals to attract each other, repel each other, sense their local cell density, sense whether the nearby cells are starving or stressed, count themselves to organize the formation of structures containing a regulated number of cells, sense the volume they are in, and organize their multicellular development. Although we are probably just beginning to learn what the cells are telling each other, the elucidation of Dictyostelium extracellular signals has already led to the development of possible therapeutics for human diseases.
“…This can easily be solved with a few lines of code, and to calculate [x] at a point A in or near a community of cells (Fig. 1), a few more lines of code can sum the contribution from every cell in the community to the local concentration of x at point A [26,27]. A simple albeit somewhat messy correction can then be made to adjust for the presence of receptors for x on cells, which by binding x reduce the concentration of x [26].…”
Section: Resultsmentioning
confidence: 99%
“…A recombinant version of the factor also acted as a chemorepellent in gradient chambers [30], but to make sure we were using biologically relevant gradients, we did concentration calculations as described above to determine the physiological concentration range and slope (d[x]/dr), where r is the distance moving radially outwards from the colony (Fig. 2A) [27]. Fig.…”
Microbial communities are the simplest possible model of multicellular tissues, allowing studies of cell-cell interactions to be done with as few extraneous factors as possible. For instance, the eukaryotic microbe
Dictyostelium discoideum
proliferates as single cells, and when starved, the cells aggregate together and form structures of ~20,000 cells. The cells use a variety of signals to direct their movement, inform each other of their local cell density and whether they are starving, and organize themselves into groups of ~20,000 cells. Mathematical models and computational approaches have been a key check on, and guide of, the experimental work. In this minireview, I will discuss diffusion calculations and Monte Carlo simulations that were used for
Dictyostelium
studies that offer general paradigms for several aspects of cell-cell communication. For instance, computational work showed that diffusible secreted cell-density sensing (quorum) factors can diffuse away so quickly from a single cell that the local concentration will not build up to incorrectly cause the cell to sense that it is in the presence of a high density of other cells secreting that signal. In another example, computation correctly predicted a mechanism that allows a group of cells to break up into subgroups. These are thus some examples of the power and necessity of computational work in biology.
Some extracellular glycoconjugates have sialic acid as the terminal sugar, and sialidases are enzymes that remove this sugar. Mammals have 4 sialidases and can be elevated in inflammation and fibrosis. In this report, we show that incubation of human neutrophils with the extracellular human sialidase NEU3, but not NEU1, NEU2 or NEU4, induces human male and female neutrophils to change from a round to a more amoeboid morphology, causes the primed human neutrophil markers CD11b, CD18, and CD66a to localize to the cell cortex, and decreases the localization of the unprimed human neutrophil markers CD43 and CD62-L at the cell cortex. NEU3, but not the other 3 sialidases, also causes human male and female neutrophils to increase their F-actin content. Human neutrophils treated with NEU3 show a decrease in cortical levels of Sambucus nigra lectin staining and an increase in cortical levels of peanut agglutinin staining, indicating a NEU3-induced desialylation. The inhibition of NEU3 by the NEU3 inhibitor 2-acetylpyridine attenuated the NEU3 effect on neutrophil morphology, indicating that the effect of NEU3 is dependent on its enzymatic activity. Together, these results indicate that NEU3 can prime human male and female neutrophils, and that NEU3 is a potential regulator of inflammation.
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