scholarly journals MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Uschi Lindert ◽  
Wayne A. Cabral ◽  
Surasawadee Ausavarat ◽  
Siraprapa Tongkobpetch ◽  
Katja Ludin ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Intramembrane Proteolysis ◽  
Regulated Intramembrane Proteolysis

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.

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.

scholarly journals MAG Induces Regulated Intramembrane Proteolysis of the p75 Neurotrophin Receptor to Inhibit Neurite Outgrowth

Neuron ◽  
2005 ◽  
Vol 46 (6) ◽  
pp. 849-855 ◽  
Author(s):  
Marco Domeniconi ◽  
Niccolò Zampieri ◽  
Tim Spencer ◽  
Melissa Hilaire ◽  
Wilfredo Mellado ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Intramembrane Proteolysis ◽  
Regulated Intramembrane Proteolysis
Sign in / Sign up

Export Citation Format

Share Document