scholarly journals Different Heterotrimeric G Protein Dynamics for Wide-Range Chemotaxis in Eukaryotic Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yoichiro Kamimura ◽  
Masahiro Ueda
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Spatial Information ◽  
Background Concentration ◽  
Gradient Sensing ◽  
Heterotrimeric G Protein ◽  
Gpcr Signaling ◽  
Chemical Gradients ◽  
Wide Range ◽  
Spatial Differences

Chemotaxis describes directional motility along ambient chemical gradients and has important roles in human physiology and pathology. Typical chemotactic cells, such as neutrophils and Dictyostelium cells, can detect spatial differences in chemical gradients over a background concentration of a 105 scale. Studies of Dictyostelium cells have elucidated the molecular mechanisms of gradient sensing involving G protein coupled receptor (GPCR) signaling. GPCR transduces spatial information through its cognate heterotrimeric G protein as a guanine nucleotide change factor (GEF). More recently, studies have revealed unconventional regulation of heterotrimeric G protein in the gradient sensing. In this review, we explain how multiple mechanisms of GPCR signaling ensure the broad range sensing of chemical gradients in Dictyostelium cells as a model for eukaryotic chemotaxis.

scholarly journals Yeast G-proteins mediate directional sensing and polarization behaviors in response to changes in pheromone gradient direction

2013 ◽  
Vol 24 (4) ◽  
pp. 521-534 ◽  
Author(s):  
Travis I. Moore ◽  
Hiromasa Tanaka ◽  
Hyung Joon Kim ◽  
Noo Li Jeon ◽  
Tau-Mu Yi
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Cell Polarity ◽  
Yeast Cells ◽  
Dependent Manner ◽  
Protein Activity ◽  
Gradient Sensing ◽  
Heterotrimeric G Protein ◽  
Low Concentrations ◽  
High Concentrations

Yeast cells polarize by projecting up mating pheromone gradients, a classic cell polarity behavior. However, these chemical gradients may shift direction. We examine how yeast cells sense and respond to a 180o switch in the direction of microfluidically generated pheromone gradients. We identify two behaviors: at low concentrations of α-factor, the initial projection grows by bending, whereas at high concentrations, cells form a second projection toward the new source. Mutations that increase heterotrimeric G-protein activity expand the bending-growth morphology to high concentrations; mutations that increase Cdc42 activity result in second projections at low concentrations. Gradient-sensing projection bending requires interaction between Gβγ and Cdc24, whereas gradient-nonsensing projection extension is stimulated by Bem1 and hyperactivated Cdc42. Of interest, a mutation in Gα affects both bending and extension. Finally, we find a genetic perturbation that exhibits both behaviors. Overexpression of the formin Bni1, a component of the polarisome, makes both bending-growth projections and second projections at low and high α-factor concentrations, suggesting a role for Bni1 downstream of the heterotrimeric G-protein and Cdc42 during gradient sensing and response. Thus we demonstrate that G-proteins modulate in a ligand-dependent manner two fundamental cell-polarity behaviors in response to gradient directional change.

scholarly journals How receptor diffusion influences gradient sensing

2015 ◽  
Vol 12 (102) ◽  
pp. 20141097 ◽  
Author(s):  
H. Nguyen ◽  
P. Dayan ◽  
G. J. Goodhill
Keyword(s):  
Fisher Information ◽  
Diffusion Constant ◽  
Theoretical Models ◽  
Eukaryotic Cells ◽  
Biological Processes ◽  
Directed Motion ◽  
Gradient Sensing ◽  
Chemical Gradients ◽  
Physical Limit ◽  
Spatial Differences

Chemotaxis, or directed motion in chemical gradients, is critical for various biological processes. Many eukaryotic cells perform spatial sensing, i.e. they detect gradients by comparing spatial differences in binding occupancy of chemosensory receptors across their membrane. In many theoretical models of spatial sensing, it is assumed, for the sake of simplicity, that the receptors concerned do not move. However, in reality, receptors undergo diverse modes of diffusion, and can traverse considerable distances in the time it takes such cells to turn in an external gradient. This sets a physical limit on the accuracy of spatial sensing, which we explore using a model in which receptors diffuse freely over the membrane. We find that the Fisher information carried in binding and unbinding events decreases monotonically with the diffusion constant of the receptors.

Coupling Mechanism of a GPCR and a Heterotrimeric G Protein During Chemoattractant Gradient Sensing in Dictyostelium

2010 ◽  
Vol 3 (141) ◽  
pp. ra71-ra71 ◽  
Author(s):  
X. Xu ◽  
T. Meckel ◽  
J. A. Brzostowski ◽  
J. Yan ◽  
M. Meier-Schellersheim ◽  
...  
Keyword(s):  
G Protein ◽  
Coupling Mechanism ◽  
Gradient Sensing ◽  
Heterotrimeric G Protein

scholarly journals Heterotrimeric G-protein shuttling via Gip1 extends the dynamic range of eukaryotic chemotaxis

2016 ◽  
Vol 113 (16) ◽  
pp. 4356-4361 ◽  
Author(s):  
Yoichiro Kamimura ◽  
Yukihiro Miyanaga ◽  
Masahiro Ueda
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Dynamic Range ◽  
Protein Translocation ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Heterotrimeric G Protein ◽  
Range Sensing ◽  
Interacting Protein ◽  
Wide Range

Chemotactic eukaryote cells can sense chemical gradients over a wide range of concentrations via heterotrimeric G-protein signaling; however, the underlying wide-range sensing mechanisms are only partially understood. Here we report that a novel regulator of G proteins, G protein-interacting protein 1 (Gip1), is essential for extending the chemotactic range of Dictyostelium cells. Genetic disruption of Gip1 caused severe defects in gradient sensing and directed cell migration at high but not low concentrations of chemoattractant. Also, Gip1 was found to bind and sequester G proteins in cytosolic pools. Receptor activation induced G-protein translocation to the plasma membrane from the cytosol in a Gip1-dependent manner, causing a biased redistribution of G protein on the membrane along a chemoattractant gradient. These findings suggest that Gip1 regulates G-protein shuttling between the cytosol and the membrane to ensure the availability and biased redistribution of G protein on the membrane for receptor-mediated chemotactic signaling. This mechanism offers an explanation for the wide-range sensing seen in eukaryotic chemotaxis.

Heterotrimeric G proteins in heart disease

2000 ◽  
Vol 78 (3) ◽  
pp. 187-198 ◽  
Author(s):  
Oliver Zolk ◽  
Ichiro Kouchi ◽  
Petra Schnabel ◽  
Michael Böhm
Keyword(s):  
Heart Failure ◽  
G Protein ◽  
G Proteins ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Heart Diseases ◽  
Membrane Receptors ◽  
Adrenergic System ◽  
Heterotrimeric G Proteins ◽  
Heterotrimeric G Protein

Guanine nucleotide binding proteins (G proteins) are largely grouped into three classes: heterotrimeric G proteins, ras-like or small molecular weight GTP binding proteins, and others like Gh. In the heart G proteins transduce signals from a variety of membrane receptors to generate diverse effects on contractility, heart rate, and myocyte growth. This central position of G proteins forming a switchboard between extracellular signals and intracellular effectors makes them candidates possibly involved in the pathogenesis of cardiac hypertrophy, heart failure, and arrhythmia. This review focuses primarily on discoveries of heterotrimeric G protein alterations in heart diseases that help us to understand the pathogenesis and pathophysiology. We also discuss the underlying molecular mechanisms of heterotrimeric G protein signalling.Key words: G proteins, signal transduction, adrenergic system, heart failure, hypertrophy.

scholarly journals Polarization of the Yeast Pheromone Receptor Requires Its Internalization but Not Actin-dependent Secretion

2010 ◽  
Vol 21 (10) ◽  
pp. 1737-1752 ◽  
Author(s):  
Dmitry V. Suchkov ◽  
Reagan DeFlorio ◽  
Edward Draper ◽  
Amber Ismael ◽  
Madhushalini Sukumar ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
G Protein ◽  
Protein Localization ◽  
Receptor Internalization ◽  
Gradient Sensing ◽  
Pheromone Receptor ◽  
Surface Receptors ◽  
Chemical Gradients ◽  
Actin Cables ◽  
Mating Projection

In the best understood models of eukaryotic directional sensing, chemotactic cells maintain a uniform distribution of surface receptors even when responding to chemical gradients. The yeast pheromone receptor is also uniformly distributed on the plasma membrane of vegetative cells, but pheromone induces its polarization into “crescents” that cap the future mating projection. Here, we find that in pheromone-treated cells, receptor crescents are visible before detectable polarization of actin cables and that the receptor can polarize in the absence of actin-dependent directed secretion. Receptor internalization, in contrast, seems to be essential for the generation of receptor polarity, and mutations that deregulate this process confer dramatic defects in directional sensing. We also show that pheromone induces the internalization and subsequent polarization of the mating-specific Gα and Gβ proteins and that the changes in G protein localization depend on receptor internalization and receptor–Gα coupling. Our data suggest that the polarization of the receptor and its G protein precedes actin polarization and is important for gradient sensing. We propose that the establishment of receptor/G protein polarity depends on a novel mechanism involving differential internalization and that this serves to amplify the shallow gradient of activated receptor across the cell.

scholarly journals GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis

2017 ◽  
Vol 114 (47) ◽  
pp. E10092-E10101 ◽  
Author(s):  
Xuehua Xu ◽  
Xi Wen ◽  
Douwe M. Veltman ◽  
Ineke Keizer-Gunnink ◽  
Henderikus Pots ◽  
...  
Keyword(s):  
Long Range ◽  
Molecular Mechanisms ◽  
Leading Edge ◽  
Negative Regulator ◽  
Ras Signaling ◽  
Gradient Sensing ◽  
Membrane Recruitment ◽  
Inhibitory Processes ◽  
Ras Activation ◽  
Wide Range

Eukaryotic cells chemotax in a wide range of chemoattractant concentration gradients, and thus need inhibitory processes that terminate cell responses to reach adaptation while maintaining sensitivity to higher-concentration stimuli. However, the molecular mechanisms underlying inhibitory processes are still poorly understood. Here, we reveal a locally controlled inhibitory process in a GPCR-mediated signaling network for chemotaxis inDictyostelium discoideum. We identified a negative regulator of Ras signaling, C2GAP1, which localizes at the leading edge of chemotaxing cells and is activated by and essential for GPCR-mediated Ras signaling. We show that both C2 and GAP domains are required for the membrane targeting of C2GAP1, and that GPCR-triggered Ras activation is necessary to recruit C2GAP1 from the cytosol and retains it on the membrane to locally inhibit Ras signaling. C2GAP1-deficientc2gapA−cells have altered Ras activation that results in impaired gradient sensing, excessive polymerization of F actin, and subsequent defective chemotaxis. Remarkably, these cellular defects ofc2gapA−cells are chemoattractant concentration dependent. Thus, we have uncovered an inhibitory mechanism required for adaptation and long-range chemotaxis.

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