scholarly journals BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts

2004 ◽  
Vol 167 (6) ◽  
pp. 1205-1215 ◽  
Author(s):  
Shingo Suzuki ◽  
Tadahiro Numakawa ◽  
Kazuhiro Shimazu ◽  
Hisatsugu Koshimizu ◽  
Tomoko Hara ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Plasma Membranes ◽  
Hippocampal Slices ◽  
Synaptic Response ◽  
Signaling Mechanism ◽  
Synaptic Modulation ◽  
Signaling Mechanisms ◽  
The Central Nervous System ◽  
Trk Inhibitors

Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity but the underlying signaling mechanisms remain unknown. Here, we show that BDNF rapidly recruits full-length TrkB (TrkB-FL) receptor into cholesterol-rich lipid rafts from nonraft regions of neuronal plasma membranes. Translocation of TrkB-FL was blocked by Trk inhibitors, suggesting a role of TrkB tyrosine kinase in the translocation. Disruption of lipid rafts by depleting cholesterol from cell surface blocked the ligand-induced translocation. Moreover, disruption of lipid rafts prevented potentiating effects of BDNF on transmitter release in cultured neurons and synaptic response to tetanus in hippocampal slices. In contrast, lipid rafts are not required for BDNF regulation of neuronal survival. Thus, ligand-induced TrkB translocation into lipid rafts may represent a signaling mechanism selective for synaptic modulation by BDNF in the central nervous system.

scholarly journals THE ROLE OF SYNAPSIN I IN INTRACELLULAR SIGNALING MECHANISMS UNDERLIES EXERCISE-INDUCED IMPROVEMENT IN SOCIAL MEMORY: A SYSTEMATIC REVIEW

2017 ◽  
Vol 10 (9) ◽  
pp. 88
Author(s):  
Ria Margiana ◽  
Akmal Primadian Suprapto
Keyword(s):  
Cell Signaling ◽  
Intracellular Signaling ◽  
Laboratory Experiments ◽  
Biological Function ◽  
Social Memory ◽  
Synapsin I ◽  
Signaling Mechanism ◽  
Signaling Mechanisms ◽  
Exercise Induced

  Objective: Intracellular signaling mechanism is an important biological function, as scholars continue to seek new ways of improving social memory. Researchers have conducted several studies on the role of synapsin I in intracellular signaling mechanism. This study assessed the empirical evidence that shows the role of synapsin I in intracellular signaling mechanism with the aim of achieving exercise-induced improvement in social memory.Methods: Nine previously conducted researches were reviewed in this paper. The included studies were controlled laboratory experiments involving mice as the subjects.Results: Although the studies included were done in different timelines, the researchers agreed in unison that synapsin I plays a crucial role in cell signaling. The outcome of the practical studies was vital in understanding function and physiology of human cells, which is fundamental in science and human anatomy.Conclusion: In particular, the findings shows how exercise can improve social memory by triggering the intracellular signaling mechanism. The limited number of studies addressing the topic of intracellular cell signaling suggests that more study is needed to provide more evidence on the issue.

Mechanisms of membrane estrogen receptor-α-mediated rapid stimulation of Ca2+ levels and prolactin release in a pituitary cell line

2005 ◽  
Vol 288 (2) ◽  
pp. E388-E397 ◽  
Author(s):  
Nataliya N. Bulayeva ◽  
Ann L. Wozniak ◽  
L. Leanne Lash ◽  
Cheryl S. Watson
Keyword(s):  
Estrogen Receptor ◽  
Cell Line ◽  
Estrogen Receptor Α ◽  
Signaling Mechanism ◽  
Signaling Mechanisms ◽  
Intracellular Ca ◽  
A Cell ◽  
17Β Estradiol ◽  
Rapid Stimulation

The role of membrane estrogen receptor-α (mERα) in rapid nongenomic responses to 17β-estradiol (E2) was tested in sublines of GH3/B6 rat prolactinoma cells selected for high (GH3/B6/F10) and low (GH3/B6/D9) mERα expression. E2 elicited rapid, concentration-dependent intracellular Ca2+ concentration ([Ca2+]i) increases in the F10 subline. Lack of inhibition by thapsigargin depletion of intracellular Ca2+ pools, together with abrogation of the response in Ca2+-free medium, suggested an extracellular source of Ca2+ for this response. The participation of voltage-dependant channels in the E2-induced [Ca2+]i increase was confirmed by the specific L-type Ca2+ channel inhibitor nifedipine. For comparison, the D9 mERα-depleted subline was insensitive to steroid action via this signaling mechanism. [Ca2+]i elevation was correlated with prolactin (PRL) release in the F10 cell line in as little as 3 min. E2 caused a much higher PRL release than KCl treatment (which caused maximal Ca2+ elevation), suggesting that secretion was also controlled by additional mechanisms. Participation of mERα in these effects was confirmed by the ability of E2-peroxidase (a cell-impermeable analog of E2) to cause these responses, blockage of the responses with the ER antagonist ICI 182 780, and the inability of the E2 stereoisomer 17α-E2 to elicit a response. Thus rapid exocytosis of PRL is regulated in these cells by mERα signaling to specific Ca2+ channels utilizing extracellular Ca2+ sources and additional signaling mechanisms.

scholarly journals Rnd2 differentially regulates oligodendrocyte myelination at different developmental periods

2021 ◽  
pp. mbc.E20-05-0332
Author(s):  
Yuki Miyamoto ◽  
Tomohiro Torii ◽  
Miho Terao ◽  
Shuji Takada ◽  
Akito Tanoue ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Morphological Changes ◽  
Rho Kinase ◽  
Spatial And Temporal Patterns ◽  
Dynamic Cell ◽  
The Central Nervous System ◽  
Myelin Thickness ◽  
Rho Family ◽  
Oligodendrocyte Precursor

In the central nervous system, oligodendrocyte precursor cells differentiate into oligodendrocytes to wrap their plasma membranes around neuronal axons, generating mature neural networks with myelin sheaths according to spatial and temporal patterns. While myelination is known to be one of the most dynamic cell morphological changes, the overall intrinsic and extrinsic molecular cues controlling myelination remain to be fully clarified. Here, we describe the biphasic roles of Rnd2, an atypical branch of the Rho family GTPase, in oligodendrocyte myelination during development and after maturation in mice. Compared with littermate controls, oligodendrocyte-specific Rnd2 knockout mice exhibit decreased myelin thickness at the onset of myelination but increased myelin thickness in the later period. Larger proportions of Rho kinase and its substrate Mbs, the signaling unit that negatively regulates oligodendrocyte myelination, are phosphorylated at the onset of myelination, while their smaller proportions are phosphorylated in the later period. In addition, we confirm the biphasic role of Rnd2 through experiments with oligodendrocyte-specific Rnd2 transgenic mice. We conclude that Rnd2 positively regulates myelination in the early myelinating period and negatively regulates myelination in the later period. This unique modulator thus plays different roles depending on the myelination period.

Adrenergic Pharmacology: Focus on the Central Nervous System

CNS Spectrums ◽  
2001 ◽  
Vol 6 (8) ◽  
pp. 656-662 ◽  
Author(s):  
Andre S. Pupo ◽  
Kenneth P. Minneman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Signaling Mechanisms ◽  
Treatment Of Depression ◽  
The Central Nervous System ◽  
Sleep Arousal ◽  
Obesity Hypertension ◽  
Subtype Selective ◽  
The Brain

ABSTRACTNorepinephrine and epinephrine are involved in the control of several important functions of the central nervous system (CNS), including sleep, arousal, mood, appetite, and autonomic outflow. Catecholamines control these functions through activation of a family of adrenergic receptors (ARs). The ARs are divided into three subfamilies (α1, α2, and β) based on their pharmacologic properties, signaling mechanisms, and structure. ARs in the CNS are targets for several therapeutic agents used in the treatment of depression, obesity, hypertension, and other diseases. Not much is known, however, about the role of specific AR sub-types in the actions of these drugs. In this paper, we provide an overview of adrenergic pharmacology in the CNS, focusing on the pharmacologic properties of subtype-selective AR agonists and antagonists, the accessibility of these drugs to the CNS, and the distribution of ARs in different areas of the brain.

Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas translocation into lipid rafts

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 2290-2299 ◽  
Author(s):  
Simona Moretti ◽  
Antonio Procopio ◽  
Raffaella Lazzarini ◽  
Maria Rita Rippo ◽  
Roberto Testa ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Signaling Mechanism ◽  
Agonistic Antibody ◽  
Neuropilin 1 ◽  
Lipid Raft Microdomains ◽  
Biologic Function ◽  
Necrosis Factor

Semaphorins and their receptors (plexins) have pleiotropic biologic functions, including regulation of immune responses. However, the role of these molecules inside the immune system and the signal transduction mechanism(s) they use are largely unknown. Here, we show that Semaphorin3A (Sema3A) triggers a proapoptotic program that sensitizes leukemic T cells to Fas (CD95)-mediated apoptosis. We found that Sema3A stimulation provoked Fas translocation into lipid raft microdomains before binding with agonistic antibody or FasL (CD95L). Disruption of lipid rafts reduced sensitivity to Fas-mediated apoptosis in the presence of Sema3A. Furthermore, we show that plexin-A1, together with Sema3A-binding neuropilin-1, was rapidly incorporated into membrane rafts after ligand stimulation, resulting in the transport of actin-linking proteins into Fas-enriched rafts. Cells expressing a dominant-negative mutant of plexin-A1 did not show Fas clustering and apoptosis on Sema3A/Fas costimulation. This work identifies a novel biologic function of semaphorins and presents an unexpected signaling mechanism linking semaphorin to the tumor necrosis factor family receptors.

scholarly journals Can We Design a Nogo Receptor-Dependent Cellular Therapy to Target MS?

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 1 ◽  
Author(s):  
Min Kim ◽  
Jung Kang ◽  
Paschalis Theotokis ◽  
Nikolaos Grigoriadis ◽  
Steven Petratos
Keyword(s):  
Small Molecules ◽  
Cellular Therapy ◽  
Unmet Need ◽  
Axonal Dystrophy ◽  
Signaling Mechanism ◽  
Current Review ◽  
Clinical Reality ◽  
Signaling Mechanisms ◽  
The Central Nervous System ◽  
Relapse Rates

The current landscape of therapeutics designed to treat multiple sclerosis (MS) and its pathological sequelae is saturated with drugs that modify disease course and limit relapse rates. While these small molecules and biologicals are producing profound benefits to patients with reductions in annualized relapse rates, the repair or reversal of demyelinated lesions with or without axonal damage, remains the principle unmet need for progressive forms of the disease. Targeting the extracellular pathological milieu and the signaling mechanisms that drive neurodegeneration are potential means to achieve neuroprotection and/or repair in the central nervous system of progressive MS patients. The Nogo-A receptor-dependent signaling mechanism has raised considerable interest in neurological disease paradigms since it can promulgate axonal transport deficits, further demyelination, and extant axonal dystrophy, thereby limiting remyelination. If specific therapeutic regimes could be devised to directly clear the Nogo-A-enriched myelin debris in an expedited manner, it may provide the necessary CNS environment for neurorepair to become a clinical reality. The current review outlines novel means to achieve neurorepair with biologicals that may be directed to sites of active demyelination.

scholarly journals Mechanisms of Amyloid-Beta Peptide Uptake by Neurons: The Role of Lipid Rafts and Lipid Raft-Associated Proteins

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Aaron Y. Lai ◽  
JoAnne McLaurin
Keyword(s):  
Lipid Rafts ◽  
Amyloid Beta ◽  
Lipid Raft ◽  
Pathological Feature ◽  
Beta Peptide ◽  
Associated Proteins ◽  
Potential Link ◽  
The Central Nervous System ◽  
Peptide Uptake

A hallmark pathological feature of Alzheimer's disease (AD) is the accumulation of extracellular plaques composed of the amyloid-beta (Aβ) peptide. Thus, classically experiments were designed to examine Aβtoxicities within the central nervous system (CNS) from the extracellular space. However, a significant amount of evidence now suggests that intraneuronal accumulation of Aβis neurotoxic and may play an important role in the disease progression of AD. One of the means by which neurons accumulate intracellular Aβis through uptake of extracellular Aβpeptides, and this process may be a potential link between Aβgeneration, synaptic dysfunction, and AD pathology. Recent studies have found that neuronal internalization of Aβinvolves lipid rafts and various lipid raft-associated receptor proteins. Uptake mechanisms independent of lipid rafts have also been implicated. The aim of this paper is to summarize these findings and discuss their significance in the pathogenesis of AD.

scholarly journals MIRNAS in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity

2016 ◽  
Vol 10s1 ◽  
pp. JEN.S39916 ◽  
Author(s):  
Carlos Lafourcade ◽  
Juan Pablo Ramírez ◽  
Alejandro Luarte ◽  
Anilely Fernández ◽  
Ursula Wyneken
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Multivesicular Body ◽  
Neuronal Morphology ◽  
Multivesicular Bodies ◽  
Neuronal Function ◽  
Signaling Mechanism ◽  
Pathological Conditions ◽  
The Central Nervous System

Astrocytes use gliotransmitters to modulate neuronal function and plasticity. However, the role of small extracellular vesicles, called exosomes, in astrocyte-to-neuron signaling is mostly unknown. Exosomes originate in multivesicular bodies of parent cells and are secreted by fusion of the multivesicular body limiting membrane with the plasma membrane. Their molecular cargo, consisting of RNA species, proteins, and lipids, is in part cell type and cell state specific. Among the RNA species transported by exosomes, microRNAs (miRNAs) are able to modify gene expression in recipient cells. Several miRNAs present in astrocytes are regulated under pathological conditions, and this may have far-reaching consequences if they are loaded in exosomes. We propose that astrocyte-derived miRNA-loaded exosomes, such as miR-26a, are dysregulated in several central nervous system diseases; thus potentially controlling neuronal morphology and synaptic transmission through validated and predicted targets. Unraveling the contribution of this new signaling mechanism to the maintenance and plasticity of neuronal networks will impact our understanding on the physiology and pathophysiology of the central nervous system.

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