Synthesizing genetic clock with toggle switch and oscillator

2014 ◽  
Author(s):  
Po-Kuei Chen ◽  
Chun-Liang Lin
Keyword(s):  
Toggle Switch

scholarly journals Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E2 receptor EP2 subtype

2021 ◽  
Vol 7 (14) ◽  
pp. eabf1268
Author(s):  
Changxiu Qu ◽  
Chunyou Mao ◽  
Peng Xiao ◽  
Qingya Shen ◽  
Ya-Ni Zhong ◽  
...  
Keyword(s):  
G Protein ◽  
Rational Design ◽  
Receptor Activation ◽  
Prostaglandin E ◽  
Toggle Switch ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Ligand Selectivity ◽  
Activation Mechanisms ◽  
Prostaglandin E2 Receptor

Selective modulation of the heterotrimeric G protein α S subunit–coupled prostaglandin E2 (PGE2) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo–electron microscopy structure of the EP2-Gs complex with its endogenous agonist PGE2 and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W6.48 “toggle switch” and coupling to Gs via helix 8. Moreover, inspection of the agonist-bound EP2 structures uncovered key motifs governing ligand selectivity. Our study provides important knowledge for agonist recognition and activation mechanisms of EP2 and will facilitate the rational design of drugs targeting the PGE2 signaling system.

scholarly journals Biological Signal Processing with a Genetic Toggle Switch

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68345 ◽  
Author(s):  
Patrick Hillenbrand ◽  
Georg Fritz ◽  
Ulrich Gerland
Keyword(s):  
Signal Processing ◽  
Toggle Switch ◽  
Biological Signal ◽  
Biological Signal Processing

scholarly journals Epigenetic control of pheromone MAPK signaling determines sexual fecundity inCandida albicans

2017 ◽  
Vol 114 (52) ◽  
pp. 13780-13785 ◽  
Author(s):  
Christine M. Scaduto ◽  
Shail Kabrawala ◽  
Gregory J. Thomson ◽  
William Scheving ◽  
Andy Ly ◽  
...  
Keyword(s):  
Candida Albicans ◽  
G Protein ◽  
Map Kinases ◽  
Mapk Pathway ◽  
Cell Types ◽  
Mapk Signaling ◽  
Toggle Switch ◽  
Β Subunit ◽  
Epigenetic Control ◽  
Incandida Albicans

Several pathogenicCandidaspecies are capable of heritable and reversible switching between two epigenetic states, “white” and “opaque.” InCandida albicans, white cells are essentially sterile, whereas opaque cells are mating-proficient. Here, we interrogate the mechanism by which the white-opaque switch regulates sexual fecundity and identify four genes in the pheromone MAPK pathway that are expressed at significantly higher levels in opaque cells than in white cells. These genes encode the β subunit of the G-protein complex (STE4), the pheromone MAPK scaffold (CST5), and the two terminal MAP kinases (CEK1/CEK2). To define the contribution of each factor to mating,C. albicanswhite cells were reverse-engineered to express elevated, opaque-like levels of these factors, either singly or in combination. We show that white cells co-overexpressingSTE4,CST5, andCEK2undergo mating four orders of magnitude more efficiently than control white cells and at a frequency approaching that of opaque cells. Moreover, engineered white cells recapitulate the transcriptional and morphological responses of opaque cells to pheromone. These results therefore reveal multiple bottlenecks in pheromone MAPK signaling in white cells and that alleviation of these bottlenecks enables efficient mating by these “sterile” cell types. Taken together, our findings establish that differential expression of several MAPK factors underlies the epigenetic control of mating inC. albicans. We also discuss how fitness advantages could have driven the evolution of a toggle switch to regulate sexual reproduction in pathogenicCandidaspecies.

Single-pole-double-throw switch based on toggle switch

2003 ◽  
Vol 39 (8) ◽  
pp. 668 ◽  
Author(s):  
B. Schauwecker ◽  
K.M. Strohm ◽  
T. Mack ◽  
W. Simon ◽  
J.-F. Luy
Keyword(s):  
Toggle Switch

Control of gene expression using a red- and far-red light–responsive bi-stable toggle switch

2014 ◽  
Vol 9 (3) ◽  
pp. 622-632 ◽  
Author(s):  
Konrad Müller ◽  
Matias D Zurbriggen ◽  
Wilfried Weber
Keyword(s):  
Gene Expression ◽  
Red Light ◽  
Toggle Switch ◽  
Control Of Gene Expression

scholarly journals Jagged–Delta asymmetry in Notch signaling can give rise to a Sender/Receiver hybrid phenotype

2015 ◽  
Vol 112 (5) ◽  
pp. E402-E409 ◽  
Author(s):  
Marcelo Boareto ◽  
Mohit Kumar Jolly ◽  
Mingyang Lu ◽  
José N. Onuchic ◽  
Cecilia Clementi ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Target Genes ◽  
Tumor Stroma ◽  
Notch Receptor ◽  
Toggle Switch ◽  
Cell Fate Determination ◽  
Asymmetric Effect ◽  
Fate Determination

Notch signaling pathway mediates cell-fate determination during embryonic development, wound healing, and tumorigenesis. This pathway is activated when the ligand Delta or the ligand Jagged of one cell interacts with the Notch receptor of its neighboring cell, releasing the Notch Intracellular Domain (NICD) that activates many downstream target genes. NICD affects ligand production asymmetrically––it represses Delta, but activates Jagged. Although the dynamical role of Notch–Jagged signaling remains elusive, it is widely recognized that Notch–Delta signaling behaves as an intercellular toggle switch, giving rise to two distinct fates that neighboring cells adopt––Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Here, we devise a specific theoretical framework that incorporates both Delta and Jagged in Notch signaling circuit to explore the functional role of Jagged in cell-fate determination. We find that the asymmetric effect of NICD renders the circuit to behave as a three-way switch, giving rise to an additional state––a hybrid Sender/Receiver (medium ligand, medium receptor). This phenotype allows neighboring cells to both send and receive signals, thereby attaining similar fates. We also show that due to the asymmetric effect of the glycosyltransferase Fringe, different outcomes are generated depending on which ligand is dominant: Delta-mediated signaling drives neighboring cells to have an opposite fate; Jagged-mediated signaling drives the cell to maintain a similar fate to that of its neighbor. We elucidate the role of Jagged in cell-fate determination and discuss its possible implications in understanding tumor–stroma cross-talk, which frequently entails Notch–Jagged communication.

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