scholarly journals Murine astrotactins 1 and 2 have similar membrane topology and mature via endoproteolytic cleavage catalyzed by signal peptidase

2018 ◽  
Author(s):  
Patricia Lara ◽  
Åsa Tellgren-Roth ◽  
Hourinaz Behesti ◽  
Zachi Horn ◽  
Nina Schiller ◽  
...  
Keyword(s):  
Receptor Trafficking ◽  
Membrane Topology ◽  
Signal Peptidase ◽  
Planar Polarity ◽  
Cellular Functions ◽  
Terminal Domain ◽  
Neuronal Membranes ◽  
Endoproteolytic Cleavage ◽  
Microsomal Membranes ◽  
The Central Nervous System

Astrotactins 1 (Astn1) and Astn2 are membrane proteins that function in glial-guided migration, receptor trafficking and synaptic plasticity in the brain, as well as in planar polarity pathways in skin. Here, we used glycosylation mapping and protease-protection approaches to map the topologies of mouse Astn1 and Astn2 in rough microsomal membranes (RMs), and found that Astn2 has a cleaved N-terminal signal peptide (SP), an N-terminal domain located in the lumen of the RMs (topologically equivalent to the extracellular surface in cells), two transmembrane helices (TMHs), and a large C-terminal lumenal domain. We also found that Astn1 has the same topology as Astn2, but we did not observe any evidence of SP cleavage in Astn1. Both Astn1 and Astn2 mature through endoproteolytic cleavage in the second TMH; importantly, we identified the endoprotease responsible for the maturation of Astn1 and Astn2 as the endoplasmic reticulum signal peptidase. Differences in the degree of Astn1 and Astn2 maturation possibly contribute to the higher levels of the C-terminal domain of Astn1 detected on neuronal membranes of the central nervous system. These differences may also explain the distinct cellular functions of Astn1 and Astn2, such as in membrane adhesion, receptor trafficking, and planar polarity signaling.

scholarly journals Murine astrotactins 1 and 2 have a similar membrane topology and mature via endoproteolytic cleavage catalyzed by a signal peptidase

2019 ◽  
Vol 294 (12) ◽  
pp. 4538-4545
Author(s):  
Patricia Lara ◽  
Åsa Tellgren-Roth ◽  
Hourinaz Behesti ◽  
Zachi Horn ◽  
Nina Schiller ◽  
...  
Keyword(s):  
Membrane Topology ◽  
Signal Peptidase ◽  
Endoproteolytic Cleavage

Hijacking cellular functions for processing and delivery of colicins E3 and D into the cytoplasm

2012 ◽  
Vol 40 (6) ◽  
pp. 1486-1491 ◽  
Author(s):  
Miklos de Zamaroczy ◽  
Liliana Mora
Keyword(s):  
Target Cell ◽  
Specific Interaction ◽  
Membrane Receptors ◽  
Signal Peptidase ◽  
Target Cells ◽  
Cellular Functions ◽  
Extracellular Medium ◽  
Inner Membrane ◽  
Molecular Events ◽  
Endoproteolytic Cleavage

The mechanisms for importing colicins from the extracellular medium into Escherichia coli target cells implicate a complex cascade of interactions with host proteins. It is known that colicins interact with membrane receptors, and they may appropriate them structurally, but not functionally, as a scaffold on the surface of the target cell so that they can be translocated across the outer membrane. During the import into the periplasm, colicins parasitize functionally membrane porins and energy-transducers by mimicking their natural substrates or interacting partners. Such structural or functional parasitism also takes place during the late molecular events responsible for the processing and translocation of nuclease colicins across the inner membrane. Two different RNase colicins (D and E3) require an endoproteolytic cleavage, dependent on the inner membrane ATPase/protease FtsH, in order to transfer their C-terminal toxic domain into the cytoplasm. Moreover, the processing of colicin D necessitates a specific interaction with the signal peptidase LepB, but without appropriating the catalytic activity of this enzyme. A comparison of the differences in structural and functional organizations of these two colicins, as well as the pore-forming colicin B, is discussed in the present paper in connection with the sequential steps of their import mechanisms and the exploitation of the machinery of the target cell.

scholarly journals Ligand-directed two-step labeling to quantify neuronal glutamate receptor trafficking

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kento Ojima ◽  
Kazuki Shiraiwa ◽  
Kyohei Soga ◽  
Tomohiro Doura ◽  
Mikiko Takato ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Receptor Trafficking ◽  
Protein Labeling ◽  
Selective Labeling ◽  
Receptor Localization ◽  
Glutamate Receptor Trafficking ◽  
Versatile Tool ◽  
The Central Nervous System ◽  
Long Lifetime

AbstractThe regulation of glutamate receptor localization is critical for development and synaptic plasticity in the central nervous system. Conventional biochemical and molecular biological approaches have been widely used to analyze glutamate receptor trafficking, especially for α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-type glutamate receptors (AMPARs). However, conflicting findings have been reported because of a lack of useful tools for analyzing endogenous AMPARs. Here, we develop a method for the rapid and selective labeling of AMPARs with chemical probes, by combining affinity-based protein labeling and bioorthogonal click chemistry under physiological temperature in culture medium. This method allows us to quantify AMPAR distribution and trafficking, which reveals some unique features of AMPARs, such as a long lifetime and a rapid recycling in neurons. This method is also successfully expanded to selectively label N-methyl-D-aspartate-type glutamate receptors. Thus, bioorthogonal two-step labeling may be a versatile tool for investigating the physiological and pathophysiological roles of glutamate receptors in neurons.

scholarly journals NEUROPROTECTIVE ROLE OF ASCORBIC ACID: ANTIOXIDANT AND NON-ANTIOXIDANT FUNCTIONS

2018 ◽  
Vol 11 (10) ◽  
pp. 30 ◽  
Author(s):  
Arun Kumar ◽  
Reena V Saini ◽  
Adesh K Saini
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glutamate Toxicity ◽  
Cellular Functions ◽  
Dietary Antioxidant ◽  
The Central Nervous System

Ascorbic acid (AA) or Vitamin C is an important antioxidant which participates in numerous cellular functions. Although in human plasma its concentration is in micromolars but it reaches millimolar concentrations in most of the human tissues. The high ascorbate cellular concentrations are generated and maintained by a specific sodium-dependent Vitamin C transporter type 2 (SVCT2, member of Slc23 family). Metabolic processes recycle Vitamin C from its oxidized forms (ascorbate) inside the cells. AA concentration is highest in the neurons of the central nervous system (CNS) of mammals, and deletion of its transporter affects mice brain and overall survival. In the CNS, intracellular ascorbate serves several functions including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxicity. SVCT2 maintains neuronal ascorbate content in CNS which has relevance for neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. As ascorbate supplements decrease infarct size in ischemia-reperfusion injury and protect neurons from oxidative damage, it is a vital dietary antioxidant. The aim of this review is to assess the role of the SVCT2 in regulating neuronal ascorbate homeostasis in CNS and the extent to which ascorbate affects brain function as an antioxidant.

Vasopressin inhibits calcium-coupled sodium efflux system in rat brain

1994 ◽  
Vol 266 (4) ◽  
pp. R1169-R1173 ◽  
Author(s):  
F. Kanda ◽  
A. I. Arieff
Keyword(s):  
Rat Brain ◽  
Neuronal Cell ◽  
Atp Synthesis ◽  
Sodium Efflux ◽  
Rat Brain Synaptosomes ◽  
Neuronal Membranes ◽  
Brain Synaptosomes ◽  
The Central Nervous System ◽  
Na Uptake

Centrally released vasopressin plays an important role in the regulation of brain water and electrolyte composition and can affect brain intracellular pH and ATP synthesis in vivo. In this study, we evaluated the effects of [Arg8]vasopressin (AVP) on the Na(+)-Ca2+ exchanger, an important pathway in the regulation of cell Ca2+ concentration. It was found that AVP inhibited the Na(+)-Ca2+ exchanger in rat brain synaptosomes. This effect was completely blocked by the vasopressin V1-receptor antagonist d(CH2)5[(O-Me) Tyr2, Arg8]vasopressin. In addition, the vasopressin V2-receptor agonist 1-desamino-8-D-arginine vasopressin had no effect on the Na(+)-Ca2+ exchanger in rat brain synaptosomes. Depletion of intracellular Ca2+ by caffeine also had no effect on the effect of AVP on the Na(+)-Ca2+ exchanger. Na+ uptake by other pathways was also evaluated. It was found that AVP had no effect on Na+ uptake by pathways other than the Na(+)-Ca2+ exchanger. It is concluded that AVP inhibits the Na(+)-Ca2+ exchanger in neuronal membranes through vasopressin V1 receptors. Since this pathway is important in the regulation of cell volume and cytosolic Ca2+ in excitable tissue, AVP may impair neuronal cell repolarization in the central nervous system.

scholarly journals Environmental and Nutritional “Stressors” and Oligodendrocyte Dysfunction: Role of Mitochondrial and Endoplasmatic Reticulum Impairment

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 553
Author(s):  
Jessica Maiuolo ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
Saverio Nucera ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Energy Production ◽  
Lipid Synthesis ◽  
Main Function ◽  
Cellular Functions ◽  
Mitochondrial Oxidative Stress ◽  
The Central Nervous System ◽  
Altered Regulation ◽  
The Brain

Oligodendrocytes are myelinating cells of the central nervous system which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, insulating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption a large amount of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions, including energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced, the myelination process is impaired. When myelination has finished, oligodendrocyte will have synthesized about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the dysfunction of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review, the induced malfunction of oligodendrocytes by harmful exogenous stimuli has been outlined. In particular, the effects of alcohol consumption and heavy metal intake are discussed. Furthermore, the response of the oligodendrocyte to excessive mitochondrial oxidative stress and to the altered regulation of the functioning of the endoplasmic reticulum will be explored.

scholarly journals Protein translocation across the endoplasmic reticulum. II. Isolation and characterization of the signal recognition particle receptor.

1982 ◽  
Vol 95 (2) ◽  
pp. 470-477 ◽  
Author(s):  
R Gilmore ◽  
P Walter ◽  
G Blobel
Keyword(s):  
Gradient Centrifugation ◽  
Signal Recognition Particle ◽  
Preceding Paper ◽  
Signal Peptidase ◽  
Receptor Interaction ◽  
Peptidase Activity ◽  
Signal Recognition ◽  
Isolation And Characterization ◽  
Cell Biol ◽  
Microsomal Membranes

The signal recognition particle (SRP)-mediated elongation arrest of the synthesis of nascent secretory proteins can be released by salt-extracted rough microsomal membranes (Walter, P., and G. Blobel, 1981, J. Cell Biol, 91:557-561). Both the arrest-releasing activity and the signal peptidase activity were solubilized from rough microsomal membranes using the nonionic detergent Nikkol in conjunction with 250 mM KOAc. Chromatography of this extract on SRP-Sepharose separated the arrest-releasing activity from the signal peptidase activity. Further purification of the arrest-releasing activity using sucrose gradient centrifugation allowed the identification of a 72,000-dalton polypeptide as the protein responsible for the activity. Based upon its affinity for SRP, we refer to the 72,000-dalton protein as the SRP receptor. A 60,000-dalton protein fragment (Meyer, D. I., and B. Dobberstein, 1980, J. Cell Biol., 87:503-508) that had been shown previously to reconstitute the translocation activity of protease-digested membranes, was shown here by peptide mapping and immunological criteria to be derived from the SRP receptor. Findings that are in part similar, and in part different from these reported here and in our preceding paper were made independently (Meyer, D. I., E. Krause, and B. Dobberstein, 1982, Nature (Lond.). 297:647-650) and the term "docking protein" was proposed for the SRP receptor. A lower membrane content of both SRP and the SRP receptor than that of membrane bound ribosomes suggests that the SRP-SRP receptor interaction may exist transiently during the formation of a ribosome-membrane junction and during translocation.

scholarly journals New Insights into ADAMTS Metalloproteases in the Central Nervous System

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 403 ◽  
Author(s):  
Yamina Mohamedi ◽  
Tania Fontanil ◽  
Teresa Cobo ◽  
Santiago Cal ◽  
Alvaro J. Obaya
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Plasticity ◽  
Axonal Guidance ◽  
Cellular Functions ◽  
Tissue Organization ◽  
The Central Nervous System ◽  
A Disintegrin And Metalloproteinase ◽  
And Migration ◽  
Neuronal Disorders

Components of the extracellular matrix (ECM) are key players in regulating cellular functions throughout the whole organism. In fact, ECM components not only participate in tissue organization but also contribute to processes such as cellular maintenance, proliferation, and migration, as well as to support for various signaling pathways. In the central nervous system (CNS), proteoglycans of the lectican family, such as versican, aggrecan, brevican, and neurocan, are important constituents of the ECM. In recent years, members of this family have been found to be involved in the maintenance of CNS homeostasis and to participate directly in processes such as the organization of perineural nets, the regulation of brain plasticity, CNS development, brain injury repair, axonal guidance, and even the altering of synaptic responses. ADAMTSs are a family of “A disintegrin and metalloproteinase with thrombospondin motifs” proteins that have been found to be involved in a multitude of processes through the degradation of lecticans and other proteoglycans. Recently, alterations in ADAMTS expression and activity have been found to be involved in neuronal disorders such as stroke, neurodegeneration, schizophrenia, and even Alzheimer’s disease, which in turn may suggest their potential use as therapeutic targets. Herein, we summarize the different roles of ADAMTSs in regulating CNS events through interactions and the degradation of ECM components (more specifically, the lectican family of proteoglycans).

Iron and calcium in the central nervous system: a close relationship in health and sickness

2008 ◽  
Vol 36 (6) ◽  
pp. 1309-1312 ◽  
Author(s):  
Ilaria Pelizzoni ◽  
Romina Macco ◽  
Daniele Zacchetti ◽  
Fabio Grohovaz ◽  
Franca Codazzi
Keyword(s):  
Iron Uptake ◽  
Cytosolic Calcium ◽  
Brain Cell ◽  
Intracellular Accumulation ◽  
Cellular Functions ◽  
System A ◽  
Close Relationship ◽  
The Central Nervous System ◽  
Iron And Calcium ◽  
Health And Sickness

Iron and calcium are required for general cellular functions, as well as for specific neuronal-related activities. However, a pathological increase in their levels favours oxidative stress and mitochondrial damage, leading to neuronal death. Neurodegeneration can thus be determined by alterations in ionic homoeostasis and/or pro-oxidative–antioxidative equilibrium, two conditions that vary significantly in different kinds of brain cell and also with aging. In the present review, we re-evaluate recent data on NTBI (non-transferrin bound iron) uptake that suggest a strict interplay with the mechanisms of calcium control. In particular, we focus on the use of common entry pathways and on the way cytosolic calcium can modulate iron entry and determine its intracellular accumulation.

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