scholarly journals RAS Nanoclusters: Dynamic Signaling Platforms Amenable to Therapeutic Intervention

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 377
Author(s):  
Que N. Van ◽  
Priyanka Prakash ◽  
Rebika Shrestha ◽  
Trent E. Balius ◽  
Thomas J. Turbyville ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Molecular Switches ◽  
Ras Proteins ◽  
Input Signals ◽  
Membrane Bound ◽  
Intracellular Signal ◽  
Lipid Environment ◽  
And Function ◽  
Clustering Behavior

RAS proteins are mutated in approximately 20% of all cancers and are generally associated with poor clinical outcomes. RAS proteins are localized to the plasma membrane and function as molecular switches, turned on by partners that receive extracellular mitogenic signals. In the on-state, they activate intracellular signal transduction cascades. Membrane-bound RAS molecules segregate into multimers, known as nanoclusters. These nanoclusters, held together through weak protein–protein and protein–lipid associations, are highly dynamic and respond to cellular input signals and fluctuations in the local lipid environment. Disruption of RAS nanoclusters results in downregulation of RAS-mediated mitogenic signaling. In this review, we discuss the propensity of RAS proteins to display clustering behavior and the interfaces that are associated with these assemblies. Strategies to therapeutically disrupt nanocluster formation or the stabilization of signaling incompetent RAS complexes are discussed.

scholarly journals Programmed ER fragmentation drives selective ER inheritance and degradation in budding yeast meiosis

2021 ◽  
Author(s):  
George M. Otto ◽  
Tia Cheunkarndee ◽  
Jessica M. Leslie ◽  
Gloria A. Brar
Keyword(s):  
Plasma Membrane ◽  
Cell Differentiation ◽  
Budding Yeast ◽  
Developmentally Regulated ◽  
Selective Degradation ◽  
Cell Plasma ◽  
Membrane Tethering ◽  
Membrane Bound ◽  
Yeast Meiosis ◽  
And Function

AbstractThe endoplasmic reticulum (ER) is a membrane-bound organelle with diverse, essential functions that rely on the maintenance of membrane shape and distribution within cells. ER structure and function are remodeled in response to changes in cellular demand, such as the presence of external stressors or the onset of cell differentiation, but mechanisms controlling ER remodeling during cell differentiation are not well understood. Here, we describe a series of developmentally regulated changes in ER morphology and composition during budding yeast meiosis, a conserved differentiation program that gives rise to gametes. During meiosis, the cortical ER undergoes fragmentation before collapsing away from the plasma membrane at anaphase II. This programmed collapse depends on the meiotic transcription factor Ndt80, conserved ER membrane structuring proteins Lnp1 and reticulons, and the actin cytoskeleton. A subset of ER is retained at the mother cell plasma membrane and excluded from gamete cells via the action of ER-plasma membrane tethering proteins. ER remodeling is coupled to ER degradation by selective autophagy, which is regulated by the developmentally timed expression of the autophagy receptor Atg40. Autophagy relies on ER collapse, as artificially targeting ER proteins to the cortically retained ER pool prevents their degradation. Thus, developmentally programmed changes in ER morphology determine the selective degradation or inheritance of ER subdomains by gametes.

scholarly journals Plasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins

2017 ◽  
Vol 292 (46) ◽  
pp. 18862-18877 ◽  
Author(s):  
Gergő Gulyás ◽  
Glória Radvánszki ◽  
Rita Matuska ◽  
András Balla ◽  
László Hunyady ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ras Proteins ◽  
And Function ◽  
Phosphatidylinositol 4

Role of diet fat in subcellular structure and function

1985 ◽  
Vol 63 (5) ◽  
pp. 546-556 ◽  
Author(s):  
M. T. Clandinin ◽  
C. J. Field ◽  
K. Hargreaves ◽  
L. Morson ◽  
E. Zsigmond
Keyword(s):  
Plasma Membrane ◽  
Cardiac Tissue ◽  
Dietary Lipid ◽  
Head Group ◽  
Polar Head Group ◽  
Mitochondrial Atpase ◽  
Membrane Composition ◽  
Lipid Environment ◽  
And Function

Current concepts of the biomembrane will be extrapolated to membranes of homeotherms to illustrate the influence of the nature of dietary lipid in nutritionally complete diets on membrane polar head group content and fatty acid composition. Utilizing animal models, the controlling influence of dietary long chain fatty acids on major lipid constituents of the mitochondrial membrane in cardiac tissue, the plasma membrane of liver, and the synaptosomal membrane in brain can be demonstrated. Diet-induced alterations in membrane composition arc associated with demonstrable changes in the function of specific membrane proteins. To illustrate this relationship, the effect of diet on mitochondrial ATPase activity and on a hormone receptor-stimulated function in the plasma membrane of the liver will be discussed. These observations suggest that the diet fat modulates enzyme functions in vivo by changing the surrounding lipid environment in the membrane.

Traffic to the endocytic compartment of plants

1989 ◽  
Vol 47 ◽  
pp. 754-755
Author(s):  
L. R. Griffing ◽  
R. D. Record ◽  
H. H. Mollenhauer
Keyword(s):  
Plasma Membrane ◽  
Golgi Complex ◽  
Fluid Phase ◽  
Multivesicular Body ◽  
Endocytic Pathway ◽  
Cationized Ferritin ◽  
Plant Protoplasts ◽  
Whole Cells ◽  
Membrane Bound ◽  
And Function

The endocytic pathway of plants has been identified and partially characterized using nonspecific membrane-bound and fluid phase probes . The function of endocytosis in plants is, however, unknown. We shall describe how ultrastructural histochemistry, immunocytochemical analyses and fluorescence imaging have been used to explore the physiology and function of the endocytic pathway in plant protoplasts and whole cells.Cationized ferritin (CF) can be used as a marker of plasma membrane uptake in plant protoplasts. Several different organelles become labeled upon exposure of protoplasts to CF: clathrin-coated vesicles (CV), the partially coated reticulum (PCR), the Golgi complex (GC), the multivesicular body (MVB), and the vacuole (V). These organelles also participate in the pathways of secretion and delivery of protein to the lysosome (vacuole). What are the sites of overlap/divergence among the secretory, endocytic and lysosomal pathways in these cells?

Regulation of plasma membrane-bound Ca(2+)-ATPase pump by inositol phosphates in rat brain

1992 ◽  
Vol 262 (3) ◽  
pp. F411-F416
Author(s):  
C. L. Fraser ◽  
P. Sarnacki
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Rat Brain ◽  
Inositol Phosphates ◽  
Stimulatory Action ◽  
Inositol 1,4,5 Trisphosphate ◽  
Membrane Bound

We have previously shown that inositol 1,4,5-trisphosphate (1,4,5-IP3) may participate in signal transduction in brain by inhibiting plasma membrane-bound Na(+)-Ca2+ exchanger. This study was therefore designed to determine whether 1,4,5-IP3 and/or inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4) might also affect Ca2+ transport by the plasma membrane Ca(2+)-ATPase pump. Our data show that 1,4,5-IP3 significantly (P less than 0.005) stimulates Ca2+ transport, whereas 1,3,4,5-IP4 significantly (P less than 0.006) inhibits transport by the pump. However, in the presence of both 1,4,5-IP3 and 1,3,4,5-IP4, the stimulatory effect of 1,4,5-IP3 is dominant. Thus Ca2+ transport was significantly stimulated as though 1,4,5-IP3 alone was present. We also observed that 1,3,4-IP3, which had no effect on Ca2+ transport by itself, antagonizes the stimulatory action of 1,4,5-IP3 and potentiates the inhibition of Ca2+ transport by 1,3,4,5-IP4. Half-maximal activities were observed at 10(-8) M. Our data suggest that 1,3,4,5-IP4, 1,4,5-IP3, and 1,3,4-IP3 may participate in signal transduction in brain by regulating the plasma membrane-bound Ca(2+)-ATPase pump.

Photoactivatable Synthetic Ras Proteins: “Baits” for the Identification of Plasma-Membrane-Bound Binding Partners of Ras

2002 ◽  
Vol 41 (14) ◽  
pp. 2546-2550 ◽  
Author(s):  
Jürgen Kuhlmann ◽  
Andreas Tebbe ◽  
Martin Völkert ◽  
Melanie Wagner ◽  
Koji Uwai ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ras Proteins ◽  
Binding Partners ◽  
Membrane Bound

scholarly journals Ras plasma membrane signalling platforms

2005 ◽  
Vol 389 (1) ◽  
pp. 1-11 ◽  
Author(s):  
John F. HANCOCK ◽  
Robert G. PARTON
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Cell Signalling ◽  
Dynamic Structure ◽  
Signal Transduction Pathways ◽  
Ras Proteins ◽  
Complex Dynamic ◽  
Additional Level ◽  
Ras Signal Transduction

The plasma membrane is a complex, dynamic structure that provides platforms for the assembly of many signal transduction pathways. These platforms have the capacity to impose an additional level of regulation on cell signalling networks. In this review, we will consider specifically how Ras proteins interact with the plasma membrane. The focus will be on recent studies that provide novel spatial and dynamic insights into the micro-environments that different Ras proteins utilize for signal transduction. We will correlate these recent studies suggesting Ras proteins might operate within a heterogeneous plasma membrane with earlier biochemical work on Ras signal transduction.

scholarly journals Comparative de novo transcriptome analysis identifies salinity stress responsive genes and metabolic pathways in sugarcane and its wild relative Erianthus arundinaceus [Retzius] Jeswiet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
P. Vignesh ◽  
C. Mahadevaiah ◽  
R. Parimalan ◽  
R. Valarmathi ◽  
S. Dharshini ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Transcriptome Analysis ◽  
Metabolic Pathways ◽  
De Novo ◽  
Biological Processes ◽  
Wild Relative ◽  
De Novo Transcriptome ◽  
Membrane Bound ◽  
And Control

AbstractErianthus arundinaceus [Retzius] Jeswiet, a wild relative of sugarcane has a high biomass production potential and a reservoir of many genes for superior agronomic traits and tolerance to biotic and abiotic stresses. A comparative physiological, anatomical and root transcriptome analysis were carried out to identify the salt-responsive genes and metabolic pathways associated with salt-tolerant E. arundinaceus genotype IND99-907 and salinity-sensitive sugarcane genotype Co 97010. IND99-907 recorded growth of young leaves, higher proline content, higher relative water content, intact root anatomical structures and lower Na+/K+, Ca2+/K+ and Mg2+/K+ ratio as compared to the sugarcane genotype Co 97010. We have generated four de novo transcriptome assemblies between stressed and control root samples of IND99-907 and Co 97010. A total of 649 and 501 differentially expressed genes (FDR<0.01) were identified from the stressed and control libraries of IND99-907 and Co 97010 respectively. Genes and pathways related to early stress-responsive signal transduction, hormone signalling, cytoskeleton organization, cellular membrane stabilization, plasma membrane-bound calcium and proton transport, sodium extrusion, secondary metabolite biosynthesis, cellular transporters related to plasma membrane-bound trafficking, nucleobase transporter, clathrin-mediated endocytosis were highly enriched in IND99-907. Whereas in Co 97010, genes related to late stress-responsive signal transduction, electron transport system, senescence, protein degradation and programmed cell death, transport-related genes associated with cellular respiration and mitochondrial respiratory chain, vesicular trafficking, nitrate transporter and fewer secondary metabolite biosynthetic genes were highly enriched. A total of 27 pathways, 24 biological processes, three molecular functions and one cellular component were significantly enriched (FDR≤ 0.05) in IND99-907 as compared to 20 pathways, two biological processes without any significant molecular function and cellular components in Co 97010, indicates the unique and distinct expression pattern of genes and metabolic pathways in both genotypes. The genomic resources developed from this study is useful for sugarcane crop improvement through development of genic SSR markers and genetic engineering approaches.

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