Membrane proteases and tetraspanins

2011 ◽  
Vol 39 (2) ◽  
pp. 541-546 ◽  
Author(s):  
María Yáñez-Mó ◽  
Francisco Sánchez-Madrid ◽  
Carlos Cabañas
Keyword(s):  
Plasma Membrane ◽  
Cross Talk ◽  
Signalling Pathways ◽  
Local Concentration ◽  
Matrix Degradation ◽  
Adhesion Receptors ◽  
Intramembrane Proteolysis ◽  
Regulated Intramembrane Proteolysis ◽  
Protein Shedding ◽  
Internalization Rate

TEMs (tetraspanin-enriched microdomains) are specialized platforms in the plasma membrane that include adhesion receptors and enzymes. Insertion into TEMs dictates the local concentration of these molecules, regulates their internalization rate, their interaction and cross-talk with other receptors at the plasma membrane and provides links with certain signalling pathways. We focus on the associations described for tetraspanins with membrane proteases and their substrates, reviewing the emerging evidence in the literature that suggests that TEMs might be essential platforms for regulating protein shedding, RIP (regulated intramembrane proteolysis) and matrix degradation and assembly.

scholarly journals Sodium channel β1 subunits are post-translationally modified by tyrosine phosphorylation, S-palmitoylation, and regulated intramembrane proteolysis

2020 ◽  
Vol 295 (30) ◽  
pp. 10380-10393 ◽  
Author(s):  
Alexandra A. Bouza ◽  
Julie M. Philippe ◽  
Nnamdi Edokobi ◽  
Alexa M. Pinsky ◽  
James Offord ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Sodium Channel ◽  
Tyrosine Phosphorylation ◽  
Sodium Current ◽  
Epileptic Encephalopathy ◽  
Proteolytic Processing ◽  
Loss Of Function ◽  
Post Translational Modification ◽  
Intramembrane Proteolysis ◽  
Regulated Intramembrane Proteolysis

Voltage-gated sodium channel (VGSC) β1 subunits are multifunctional proteins that modulate the biophysical properties and cell-surface localization of VGSC α subunits and participate in cell–cell and cell–matrix adhesion, all with important implications for intracellular signal transduction, cell migration, and differentiation. Human loss-of-function variants in SCN1B, the gene encoding the VGSC β1 subunits, are linked to severe diseases with high risk for sudden death, including epileptic encephalopathy and cardiac arrhythmia. We showed previously that β1 subunits are post-translationally modified by tyrosine phosphorylation. We also showed that β1 subunits undergo regulated intramembrane proteolysis via the activity of β-secretase 1 and γ-secretase, resulting in the generation of a soluble intracellular domain, β1-ICD, which modulates transcription. Here, we report that β1 subunits are phosphorylated by FYN kinase. Moreover, we show that β1 subunits are S-palmitoylated. Substitution of a single residue in β1, Cys-162, to alanine prevented palmitoylation, reduced the level of β1 polypeptides at the plasma membrane, and reduced the extent of β1-regulated intramembrane proteolysis, suggesting that the plasma membrane is the site of β1 proteolytic processing. Treatment with the clathrin-mediated endocytosis inhibitor, Dyngo-4a, re-stored the plasma membrane association of β1-p.C162A to WT levels. Despite these observations, palmitoylation-null β1-p.C162A modulated sodium current and sorted to detergent-resistant membrane fractions normally. This is the first demonstration of S-palmitoylation of a VGSC β subunit, establishing precedence for this post-translational modification as a regulatory mechanism in this protein family.

Regulated intramembrane proteolysis: emergent role in cell signalling pathways

2017 ◽  
Vol 45 (6) ◽  
pp. 1185-1202 ◽  
Author(s):  
Aonghus J. McCarthy ◽  
Caroline Coleman-Vaughan ◽  
Justin V. McCarthy
Keyword(s):  
Cell Signalling ◽  
Signalling Pathways ◽  
Tumour Necrosis Factor Receptor ◽  
Intramembrane Proteolysis ◽  
Receptor Signalling ◽  
Regulated Intramembrane Proteolysis ◽  
Specific Receptors ◽  
Membrane Bound

Receptor signalling events including those initiated following activation of cytokine and growth factor receptors and the well-characterised death receptors (tumour necrosis factor receptor, type 1, FasR and TRAIL-R1/2) are initiated at the cell surface through the recruitment and formation of intracellular multiprotein signalling complexes that activate divergent signalling pathways. Over the past decade, research studies reveal that many of these receptor-initiated signalling events involve the sequential proteolysis of specific receptors by membrane-bound proteases and the γ-secretase protease complexes. Proteolysis enables the liberation of soluble receptor ectodomains and the generation of intracellular receptor cytoplasmic domain fragments. The combined and sequential enzymatic activity has been defined as regulated intramembrane proteolysis and is now a fundamental signal transduction process involved in the termination or propagation of receptor signalling events. In this review, we discuss emerging evidence for a role of the γ-secretase protease complexes and regulated intramembrane proteolysis in cell- and immune-signalling pathways.

scholarly journals Cross-talk between ethylene and drought signalling pathways is mediated by the sunflower Hahb-4 transcription factor

2006 ◽  
Vol 48 (1) ◽  
pp. 125-137 ◽  
Author(s):  
Pablo A. Manavella ◽  
Agustín L. Arce ◽  
Carlos A. Dezar ◽  
Frédérique Bitton ◽  
Jean-Pierre Renou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cross Talk ◽  
Signalling Pathways

scholarly journals Cross Talk between Sphingolipids and Glycerophospholipids in the Establishment of Plasma Membrane Asymmetry

2004 ◽  
Vol 15 (11) ◽  
pp. 4949-4959 ◽  
Author(s):  
Akio Kihara ◽  
Yasuyuki Igarashi
Keyword(s):  
Plasma Membrane ◽  
Cross Talk ◽  
Abc Transporters ◽  
Transcriptional Factor ◽  
Drug Efflux ◽  
Lipid Asymmetry ◽  
Membrane Asymmetry ◽  
P Type ◽  
Yeast Mutants ◽  
Long Chain

Glycerophospholipids and sphingolipids are distributed asymmetrically between the two leaflets of the lipid bilayer. Recent studies revealed that certain P-type ATPases and ATP-binding cassette (ABC) transporters are involved in the inward movement (flip) and outward movement (flop) of glycerophospholipids, respectively. In this study of phytosphingosine (PHS)-resistant yeast mutants, we isolated mutants for PDR5, an ABC transporter involved in drug efflux as well as in the flop of phosphatidylethanolamine. The pdr5 mutants exhibited an increase in the efflux of sphingoid long-chain bases (LCBs). Genetic analysis revealed that the PHS-resistant phenotypes exhibited by the pdr5 mutants were dependent on Rsb1p, a putative LCB-specific transporter/translocase. We found that the expression of Rsb1p was increased in the pdr5 mutants. We also demonstrated that expression of RSB1 is under the control of the transcriptional factor Pdr1p. Expression of Rsb1p also was enhanced in mutants for the genes involved in the flip of glycerophospholipids, including ROS3, DNF1, and DNF2. These results suggest that altered glycerophospholipid asymmetry induces the expression of Rsb1p. Conversely, overexpression of Rsb1p resulted in increased flip and decreased flop of fluorescence-labeled glycerophospholipids. Thus, there seems to be cross talk between sphingolipids and glycerophospholipids in maintaining the functional lipid asymmetry of the plasma membrane.

scholarly journals 277 CROSS-TALK BETWEEN TGF AND IL-1 SIGNALLING PATHWAYS: INVOLVEMENT IN OSTEOARTHRITIS

2010 ◽  
Vol 18 ◽  
pp. S124
Author(s):  
C. Bauge ◽  
S. Leclercq ◽  
P. Galera ◽  
K. Boumediene
Keyword(s):  
Cross Talk ◽  
Signalling Pathways

P2X7 receptor cross-talk regulates ATP-induced pannexin 1 internalization

2017 ◽  
Vol 474 (13) ◽  
pp. 2133-2144 ◽  
Author(s):  
Andrew K.J. Boyce ◽  
Leigh Anne Swayne
Keyword(s):  
Nervous System ◽  
Cross Talk ◽  
Purinergic Receptors ◽  
Atp Release ◽  
Extracellular Atp ◽  
Signalling Pathways ◽  
Physical Interaction ◽  
Cell Periphery ◽  
Dependent Manner ◽  
Pannexin 1

In the nervous system, extracellular ATP levels transiently increase in physiological and pathophysiological circumstances, effecting key signalling pathways in plasticity and inflammation through purinergic receptors. Pannexin 1 (Panx1) forms ion- and metabolite-permeable channels that mediate ATP release and are particularly enriched in the nervous system. Our recent study demonstrated that elevation of extracellular ATP triggers Panx1 internalization in a concentration- and time-dependent manner. Notably, this effect was sensitive to inhibition of ionotropic P2X7 purinergic receptors (P2X7Rs). Here, we report our novel findings from the detailed investigation of the mechanism underlying P2X7R–Panx1 cross-talk in ATP-stimulated internalization. We demonstrate that extracellular ATP triggers and is required for the clustering of P2X7Rs and Panx1 on Neuro2a cells through an extracellular physical interaction with the Panx1 first extracellular loop (EL1). Importantly, disruption of P2X7R–Panx1 clustering by mutation of tryptophan 74 within the Panx1 EL1 inhibits Panx1 internalization. Notably, P2X7R–Panx1 clustering and internalization are independent of P2X7R-associated intracellular signalling pathways (Ca2+ influx and Src activation). Further analysis revealed that cholesterol is required for ATP-stimulated P2X7R–Panx1 clustering at the cell periphery. Taken together, our data suggest that extracellular ATP induces and is required for Panx1 EL1-mediated, cholesterol-dependent P2X7R–Panx1 clustering and endocytosis. These findings have important implications for understanding the role of Panx1 in the nervous system and provide important new insights into Panx1–P2X7R cross-talk.

Regulation of neurogenesis and cerebral angiogenesis by cell protein proteolysis products

2021 ◽  
Vol 25 (2) ◽  
pp. 114-126
Author(s):  
E. A. Teplyashina ◽  
Y. K. Komleva ◽  
E. V. Lychkovskaya ◽  
A. S. Deikhina ◽  
A. B. Salmina
Keyword(s):  
Progenitor Cells ◽  
Neurological Deficits ◽  
Cell Protein ◽  
Synapse Elimination ◽  
Intramembrane Proteolysis ◽  
Neurogenic Niche ◽  
Regulated Intramembrane Proteolysis ◽  
Proliferation And Differentiation ◽  
Determining Factors ◽  
Stem And Progenitor Cells

Brain development is a unique process characterized by mechanisms defined as neuroplasticity (synaptogenesis, synapse elimination, neurogenesis, and cerebral angiogenesis). Numerous neurodevelopmental disorders brain damage, and aging are manifested by neurological deficits that are caused by aberrant neuroplasticity. The presence of stem and progenitor cells in neurogenic niches of the brain is responsible for the formation of new neurons capable of integrating into preexisting synaptic assemblies. The determining factors for the cells within the neurogenic niche are the activity of the vascular scaffold and the availability of active regulatory molecules that establish the optimal microenvironment. It has been found that regulated intramembrane proteolysis plays an important role in the control of neurogenesis in brain neurogenic niches. Molecules generated by the activity of specific proteases can stimulate or suppress the activity of neural stem and progenitor cells, their proliferation and differentiation, migration and integration of newly formed neurons into synaptic networks. Local neoangiogenesis supports the processes of neurogenesis in neurogenic niches, which is guaranteed by the multivalent action of peptides formed from transmembrane proteins. Identification of new molecules regulating the neuroplasticity (neurogenesis and angiogenesis). i. e. enzymes, substrates, and products of intramembrane proteolysis, will ensure the development of protocols for detecting the neuroplasticity markers and targets for efficient pharmacological modulation.

Sign in / Sign up

Export Citation Format

Share Document