Signaling pathways are focused at specialized regions of the plasma membrane by scaffolding proteins of the MAGUK family

BioEssays ◽  
1999 ◽  
Vol 21 (11) ◽  
pp. 912-921 ◽  
Author(s):  
Spiros D. Dimitratos ◽  
Daniel F. Woods ◽  
Dean G. Stathakis ◽  
Peter J. Bryant
Keyword(s):  
Plasma Membrane ◽  
Signaling Pathways ◽  
Scaffolding Proteins

scholarly journals Caveolins, a Family of Scaffolding Proteins for Organizing “Preassembled Signaling Complexes” at the Plasma Membrane

1998 ◽  
Vol 273 (10) ◽  
pp. 5419-5422 ◽  
Author(s):  
Takashi Okamoto ◽  
Amnon Schlegel ◽  
Philipp E. Scherer ◽  
Michael P. Lisanti
Keyword(s):  
Plasma Membrane ◽  
Scaffolding Proteins

scholarly journals Ykt6 membrane-to-cytosol cycling regulates exosomal Wnt secretion

2018 ◽  
Author(s):  
Karen Linnemannstöns ◽  
Pradhipa Karuna M ◽  
Leonie Witte ◽  
Jeanette Clarissa Kittel ◽  
Adi Danieli ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Long Range ◽  
Protein Trafficking ◽  
Secretory Pathway ◽  
Multivesicular Bodies ◽  
Phosphorylation Sites ◽  
Wnt Proteins ◽  
C Terminus

Protein trafficking in the secretory pathway, for example the secretion of Wnt proteins, requires tight regulation. These ligands activate Wnt signaling pathways and are crucially involved in development and disease. Wnt is transported to the plasma membrane by its cargo receptor Evi, where Wnt/Evi complexes are endocytosed and sorted onto exosomes for long-range secretion. However, the trafficking steps within the endosomal compartment are not fully understood. The promiscuous SNARE Ykt6 folds into an auto-inhibiting conformation in the cytosol, but a portion associates with membranes by its farnesylated and palmitoylated C-terminus. Here, we demonstrate that membrane detachment of Ykt6 is essential for exosomal Wnt secretion. We identified conserved phosphorylation sites within the SNARE domain of Ykt6, which block Ykt6 cycling from the membrane to the cytosol. In Drosophila, Ykt6-RNAi mediated block of Wg secretion is rescued by wildtype but not phosphomimicking Ykt6. The latter accumulates at membranes, while wildtype Ykt6 regulates Wnt trafficking between the plasma membrane and multivesicular bodies. Taken together, we show that a regulatory switch in Ykt6 fine-tunes sorting of Wnts in endosomes.

scholarly journals β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane

2020 ◽  
Vol 21 (13) ◽  
pp. 4626
Author(s):  
Barbora Melkes ◽  
Vendula Markova ◽  
Lucie Hejnova ◽  
Jiri Novotny
Keyword(s):  
Plasma Membrane ◽  
Signaling Pathways ◽  
Opioid Receptors ◽  
The Other ◽  
Hek293 Cells ◽  
Lateral Mobility ◽  
Pain Pathways ◽  
Close Cooperation ◽  
Signaling Interactions

The interactions between TRPV1 and µ-opioid receptors (MOR) have recently attracted much attention because these two receptors play important roles in pain pathways and can apparently modulate each other’s functioning. However, the knowledge about signaling interactions and crosstalk between these two receptors is still limited. In this study, we investigated the mutual interactions between MOR and TRPV1 shortly after their activation in HEK293 cells expressing these two receptors. After activation of one receptor we observed significant changes in the other receptor’s lateral mobility and vice versa. However, the changes in receptor movement within the plasma membrane were not connected with activation of the other receptor. We also observed that plasma membrane β-arrestin 2 levels were altered after treatment with agonists of both these receptors. Knockdown of β-arrestin 2 blocked all changes in the lateral mobility of both receptors. Furthermore, we found that β-arrestin 2 can play an important role in modulating the effectiveness of ERK1/2 phosphorylation after activation of MOR in the presence of TRPV1. These data suggest that β-arrestin 2 and ERK1/2 are important mediators between these two receptors and their signaling pathways. Collectively, MOR and TRPV1 can mutually affect each other’s behavior and β-arrestin 2 apparently plays a key role in the bidirectional crosstalk between these two receptors in the plasma membrane.

scholarly journals Ligands and receptors mediating signal transduction in sea urchin spermatozoa

Reproduction ◽  
2004 ◽  
Vol 127 (2) ◽  
pp. 141-149 ◽  
Author(s):  
Anna T Neill ◽  
Victor D Vacquier
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Signaling Pathways ◽  
Sea Urchin ◽  
Acrosome Reaction ◽  
Sea Urchins ◽  
Model System ◽  
Surrounding Seawater ◽  
Sea Urchin Sperm

Sea urchins have long been a model system for the study of fertilization. Much has been learned about how sea urchin sperm locate and fertilize the egg. Sperm and eggs are spawned simultaneously into the surrounding seawater. Sperm signaling pathways lead to downstream events that ensure fertilization. Upon spawning, sperm must acquire motility and then they must swim towards or respond to the egg in some way. Finally, they must undergo a terminal exocytotic event known as the acrosome reaction that allows the sperm to bind to the vitelline layer of the egg and then to fuse with the egg plasma membrane. Motility is stimulated by exposure to seawater, while later events are orchestrated by factors from the egg. The sperm signaling pathways are exquisitely tuned to bring the sperm to the egg, bind, and fuse the two cells as quickly as possible.

scholarly journals Ouabain enhances cell-cell adhesion mediated by β1-subunits of the Na+,K+-ATPase in CHO fibroblasts

2019 ◽  
Author(s):  
Claudia Andrea Vilchis-Nestor ◽  
María Luisa Roldán ◽  
Teresita Padilla-Benavides ◽  
Liora Shoshani
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Cell Adhesion Molecules ◽  
Basolateral Membrane ◽  
Adhesive Properties ◽  
Α Subunit ◽  
Cardiotonic Steroid ◽  
Pump Activity

AbstractAdhesion is an important characteristic of epithelial cells to provide a crucial barrier to pathogens and substances. In polarized epithelial cells, cell-adhesion depends on tight junctions, adherent junctions and the Na+,K+-ATPase. All these are located in the basolateral membrane of the cells. The hormone ouabain, a cardiotonic steroid, binds to the α subunit of the Na+,K+-ATPase, and inhibits the pump activity when used at above μM concentrations. At physiological nM concentrations, ouabain affects the adhesive properties of epithelial cells by inducing the expression of cell adhesion molecules through activation of signaling pathways associated to the α subunit. Our group showed that non-adherent CHO cells transfected with the canine β1subunit become adhesive, and that homotypic interactions between β1subunits of the Na+,K+-ATPase occur between neighboring epithelial cells. Therefore, in this study we investigated whether the adhesion between β1subunits was also affected by ouabain. We used CHO fibroblasts stably expressing the β1subunit of the Na+,K+-ATPase (CHO-β1) and studied the effect of ouabain on cell adhesion. Aggregation assays showed that ouabain increased the adhesion between CHO-β1cells. Immunofluorescence and biotinylation assays showed that ouabain (50 nM) increases the expression of the β1 subunit of the Na+,K+-ATPase at the cell membrane. We also screened the effect of ouabain on activation of signaling pathways in CHO-β1cells, and their effect on cell adhesion. We found that c-Src, is activated by ouabain and is therefore likely to regulate the adhesive properties of CHO-β1cells. Collectively, our findings suggest that the β1subunits adhesion is modulated by the levels of expression and activation of the Na+,K+-ATPase at the plasma membrane, which is regulated by ouabain.

scholarly journals Misregulation of Wnt Signaling Pathways at the Plasma Membrane in Brain and Metabolic Diseases

Membranes ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 844
Author(s):  
Mustafa Karabicici ◽  
Yagmur Azbazdar ◽  
Evin Iscan ◽  
Gunes Ozhan
Keyword(s):  
Plasma Membrane ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Metabolic Diseases ◽  
Wnt Signaling Pathway ◽  
Membrane Domains ◽  
Physiological Processes ◽  
Pathway Activation ◽  
Wnt Pathways ◽  
Membrane Components

Wnt signaling pathways constitute a group of signal transduction pathways that direct many physiological processes, such as development, growth, and differentiation. Dysregulation of these pathways is thus associated with many pathological processes, including neurodegenerative diseases, metabolic disorders, and cancer. At the same time, alterations are observed in plasma membrane compositions, lipid organizations, and ordered membrane domains in brain and metabolic diseases that are associated with Wnt signaling pathway activation. Here, we discuss the relationships between plasma membrane components—specifically ligands, (co) receptors, and extracellular or membrane-associated modulators—to activate Wnt pathways in several brain and metabolic diseases. Thus, the Wnt–receptor complex can be targeted based on the composition and organization of the plasma membrane, in order to develop effective targeted therapy drugs.

scholarly journals Selectivity Landscape of 100 Therapeutically Relevant GPCR Profiled by an Effector Translocation-Based BRET Platform

2020 ◽  
Author(s):  
Charlotte Avet ◽  
Arturo Mancini ◽  
Billy Breton ◽  
Christian Le Gouill ◽  
Alexander S. Hauser ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Drug Discovery ◽  
Signaling Pathways ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Systems Pharmacology ◽  
New Knowledge ◽  
Translocation Assay ◽  
Multiple Signaling ◽  
G Protein Coupled

SUMMARYThe ability of individual G protein-coupled receptors (GPCR) to engage multiple signaling pathways opens opportunities for the development of better drugs. This requires new knowledge and tools to determine the G protein subtypes and βarrestins engaged by a given receptor. Here, we used a new BRET-based effector membrane translocation assay (EMTA) that monitors activation of each Gα protein through the recruitment of selective G protein effectors and βarrestins to the plasma membrane. Profiling of 100 therapeutically relevant GPCR revealed a great diversity of coupling profiles with some receptors displaying exquisite selectivity, whereas others promiscuitely engage all four G protein families. Comparison with existing datasets points to commonalities but also to critical differences between studies. Combining a biosensor subset allowed detecting activity of nearly all GPCR thus providing a new tool for safety screens and systems pharmacology. Overall, this work describes unique resources for studying GPCR function and drug discovery.

scholarly journals Characterization of TSET, an ancient and widespread membrane trafficking complex

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Jennifer Hirst ◽  
Alexander Schlacht ◽  
John P Norcott ◽  
David Traynor ◽  
Gareth Bloomfield ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Scaffolding Proteins ◽  
Eukaryotic Evolution ◽  
Bioinformatics Tool ◽  
Membrane Turnover ◽  
Evolutionary Path ◽  
The Core ◽  
Eukaryotic Supergroup

The heterotetrameric AP and F-COPI complexes help to define the cellular map of modern eukaryotes. To search for related machinery, we developed a structure-based bioinformatics tool, and identified the core subunits of TSET, a 'missing link' between the APs and COPI. Studies in Dictyostelium indicate that TSET is a heterohexamer, with two associated scaffolding proteins. TSET is non-essential in Dictyostelium, but may act in plasma membrane turnover, and is essentially identical to the recently described TPLATE complex, TPC. However, whereas TPC was reported to be plant-specific, we can identify a full or partial complex in every eukaryotic supergroup. An evolutionary path can be deduced from the earliest origins of the heterotetramer/scaffold coat to its multiple manifestations in modern organisms, including the mammalian muniscins, descendants of the TSET medium subunits. Thus, we have uncovered the machinery for an ancient and widespread pathway, which provides new insights into early eukaryotic evolution.

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