scholarly journals GRIP1 is required for homeostatic regulation of AMPAR trafficking

2015 ◽  
Vol 112 (32) ◽  
pp. 10026-10031 ◽  
Author(s):  
Han L. Tan ◽  
Bridget N. Queenan ◽  
Richard L. Huganir
Keyword(s):  
Molecular Mechanisms ◽  
Feedback Mechanism ◽  
Homeostatic Plasticity ◽  
Homeostatic Regulation ◽  
Synaptic Scaling ◽  
Negative Feedback Mechanism ◽  
Ampar Trafficking ◽  
The Central Nervous System ◽  
Biochemical Genetic ◽  
Zona Occludens

Homeostatic plasticity is a negative feedback mechanism that stabilizes neurons during periods of perturbed activity. The best-studied form of homeostatic plasticity in the central nervous system is the scaling of excitatory synapses. Postsynaptic AMPA-type glutamate receptors (AMPARs) can be inserted into synapses to compensate for neuronal inactivity or removed to compensate for hyperactivity. However, the molecular mechanisms underlying the homeostatic regulation of AMPARs remain elusive. Here, we show that the expression of GRIP1, a multi-PDZ (postsynaptic density 95/discs large/zona occludens) domain AMPAR-binding protein, is bidirectionally altered by neuronal activity. Furthermore, we observe a subcellular redistribution of GRIP1 and a change in the binding of GRIP1 to GluA2 during synaptic scaling. Using a combination of biochemical, genetic, and electrophysiological methods, we find that loss of GRIP1 blocks the accumulation of surface AMPARs and the scaling up of synaptic strength that occur in response to chronic activity blockade. Collectively, our data point to an essential role of GRIP1-mediated AMPAR trafficking during inactivity-induced synaptic scaling.

scholarly journals Regulation of Store-Operated Ca2+ Entry by SARAF

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1887
Author(s):  
Inbal Dagan ◽  
Raz Palty
Keyword(s):  
Molecular Mechanisms ◽  
Feedback Mechanism ◽  
Cellular Biology ◽  
Excitable Cells ◽  
Major Pathway ◽  
Negative Feedback Mechanism ◽  
Crac Channels ◽  
Dependent Inactivation ◽  
Crac Channel ◽  
The One

Calcium (Ca2+) signaling plays a dichotomous role in cellular biology, controlling cell survival and proliferation on the one hand and cellular toxicity and cell death on the other. Store-operated Ca2+ entry (SOCE) by CRAC channels represents a major pathway for Ca2+ entry in non-excitable cells. The CRAC channel has two key components, the endoplasmic reticulum Ca2+ sensor stromal interaction molecule (STIM) and the plasma-membrane Ca2+ channel Orai. Physical coupling between STIM and Orai opens the CRAC channel and the resulting Ca2+ flux is regulated by a negative feedback mechanism of slow Ca2+ dependent inactivation (SCDI). The identification of the SOCE-associated regulatory factor (SARAF) and investigations of its role in SCDI have led to new functional and molecular insights into how SOCE is controlled. In this review, we provide an overview of the functional and molecular mechanisms underlying SCDI and discuss how the interaction between SARAF, STIM1, and Orai1 shapes Ca2+ signaling in cells.

Chronic intracerebroventricular CRF infusion attenuates ACTH-corticosterone release

1988 ◽  
Vol 255 (2) ◽  
pp. E213-E217 ◽  
Author(s):  
J. J. Cunningham ◽  
P. A. Meara ◽  
R. Y. Lee ◽  
H. H. Bode
Keyword(s):  
Nervous System ◽  
Adrenocorticotropic Hormone ◽  
Feedback Mechanism ◽  
Receptor Desensitization ◽  
Negative Feedback Mechanism ◽  
Corticosterone Secretion ◽  
Acute Responses ◽  
The Central Nervous System ◽  
Corticosterone Release ◽  
Pituitary Adrenal Axis

Bolus intracerebroventricular delivery of corticotropin-releasing factor (CRF) elicits acute responses of both the pituitary-adrenal axis and the sympathetic nervous system. We examined whether these stresslike responses could be maintained over a period of days by central delivery of CRF in nonstressed rats, as would be predicted if this peptide participates in the central nervous system regulation of chronic stress. CRF (4.3 or 21.5 micrograms/day) was continuously delivered into the cerebral ventricle via Alzet minipumps. In contrast to saline-infused controls, rats receiving CRF exhibited elevated excretions of corticosterone, norepinephrine, and urea nitrogen for several days. Thereafter, an attenuation of CRF responsiveness occurred when corticosterone excretion returned to basal levels despite continued central CRF infusion. However, CRF delivered intravenously during attenuation stimulated adrenocorticotropic hormone and corticosterone secretion, implicating a hypothalamic rather than pituitary locus for central CRF resistance. The present data do not permit a conclusion on whether the attenuation of the CRF response with time is the result of an ultrashort-loop negative-feedback mechanism or CRF receptor desensitization.

scholarly journals ELECTROPHYSIOLOGICAL EVIDENCE FOR THE MODULATION OF ACETYLCHOLINE RELEASE BY ENDOGENOUS ACETYLCHOLINE IN THE COCKROACH CENTRAL NERVOUS SYSTEM

1993 ◽  
Vol 175 (1) ◽  
pp. 305-311
Author(s):  
H. Le Corronc ◽  
B. Hue
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acetylcholine Receptors ◽  
Periplaneta Americana ◽  
Acetylcholinesterase Inhibitors ◽  
Feedback Mechanism ◽  
Muscarinic Acetylcholine Receptors ◽  
Negative Feedback Mechanism ◽  
Presynaptic Muscarinic Receptors ◽  
The Central Nervous System

Biochemical studies of the central nervous system (CNS) of locusts (Breer and Knipper, 1984; Knipper and Breer, 1988) have provided evidence for a muscarinic negative feedback mechanism in which muscarinic antagonists and agonists, respectively, enhance and decrease the acetylcholine (ACh) output. More recently, this inhibitory action of presynaptic muscarinic acetylcholine receptors (mAChrs) has been demonstrated in cockroach (Hue et al. 1989; Le Corronc et al. 1991) and in tobacco hornworm (Trimmer and Weeks, 1989) using electrophysiological methods. However, in insects, most experiments have not been performed under physiological conditions but in the presence of acetylcholinesterase inhibitors or exogenous agonists. The aim of this study was to determine whether the release of ACh at a central synapse in the cockroach, Periplaneta americana, could be modulated by endogenous ACh acting on presynaptic muscarinic receptors.

scholarly journals Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway

2011 ◽  
Vol 208 (10) ◽  
pp. 1963-1976 ◽  
Author(s):  
Patrick Viatour ◽  
Ursula Ehmer ◽  
Louis A. Saddic ◽  
Craig Dorrell ◽  
Jesper B. Andersen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Liver Tumors ◽  
Expression Profiles ◽  
Notch Pathway ◽  
Gene Expression Profiles ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism ◽  
Rb Pathway

Hepatocellular carcinoma (HCC) is the third cancer killer worldwide with >600,000 deaths every year. Although the major risk factors are known, therapeutic options in patients remain limited in part because of our incomplete understanding of the cellular and molecular mechanisms influencing HCC development. Evidence indicates that the retinoblastoma (RB) pathway is functionally inactivated in most cases of HCC by genetic, epigenetic, and/or viral mechanisms. To investigate the functional relevance of this observation, we inactivated the RB pathway in the liver of adult mice by deleting the three members of the Rb (Rb1) gene family: Rb, p107, and p130. Rb family triple knockout mice develop liver tumors with histopathological features and gene expression profiles similar to human HCC. In this mouse model, cancer initiation is associated with the specific expansion of populations of liver stem/progenitor cells, indicating that the RB pathway may prevent HCC development by maintaining the quiescence of adult liver progenitor cells. In addition, we show that during tumor progression, activation of the Notch pathway via E2F transcription factors serves as a negative feedback mechanism to slow HCC growth. The level of Notch activity is also able to predict survival of HCC patients, suggesting novel means to diagnose and treat HCC.

Hypotheses on physiological roles of prostaglandins.

1969 ◽  
Vol 49 (1) ◽  
pp. 122-161 ◽  
Author(s):  
E W Horton
Keyword(s):  
Linoleic Acid ◽  
Feedback Mechanism ◽  
Human Seminal Plasma ◽  
Animal Cells ◽  
Negative Feedback Mechanism ◽  
Generic Term ◽  
The Central Nervous System ◽  
Placental Blood ◽  
Fatty Acid Deficiency ◽  
And Control

Prostaglandin, a smooth muscle-stimulating depressor acidic lipid discovered int he human seminal plasma in 1935, is now used as a generic term for a family of closely related derivatives of prostanoic acid which are widely distributed in animal tissues. Prostaglandins are biosynthesized from arachidonic acid and dihomo-gamma-linolenic acid, both of which are derived from dietary linoleic acid. This finding provided a link to the observation that linoleic acid is an essential constituent of the diet. It is possible that prostaglandin compounds play a biochemical role fundamental to many, or all, animal cells. They have been implicated in sperm transport, menstruation, parturition, and control of placental blood flow. They may also play a role in the central nervous system, although this role may well be other than that of synaptic transmitter. Release of prostaglandin from various tissues is brought about by nerve stimulation. In adipose tissues, the amounts released may be sufficient to inhibit formation of cyclic AMP by the released noradrenaline, thus providing a local negative feedback mechanism. Prostaglandins also possibly play a role in muscular contractility, essential fatty acid deficiency, inhibition of lipid mobilization, atherosclerosis, and thrombosis.

scholarly journals A20 protects cells from TNF-induced apoptosis through linear ubiquitin-dependent and -independent mechanisms

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Dario Priem ◽  
Michael Devos ◽  
Sarah Druwé ◽  
Arne Martens ◽  
Karolina Slowicka ◽  
...  
Keyword(s):  
Cell Death ◽  
Complex I ◽  
Molecular Mechanisms ◽  
Feedback Mechanism ◽  
Dependent Manner ◽  
Negative Feedback Mechanism ◽  
Signaling Complex ◽  
Induced Apoptosis

Abstract The cytokine TNF promotes inflammation either directly by activating the MAPK and NF-κB signaling pathways, or indirectly by triggering cell death. A20 is a potent anti-inflammatory molecule, and mutations in the gene encoding A20 are associated with a wide panel of inflammatory pathologies, both in human and in the mouse. Binding of TNF to TNFR1 triggers the NF-κB-dependent expression of A20 as part of a negative feedback mechanism preventing sustained NF-κB activation. Apart from acting as an NF-κB inhibitor, A20 is also well-known for its ability to counteract the cytotoxic potential of TNF. However, the mechanism by which A20 mediates this function and the exact cell death modality that it represses have remained incompletely understood. In the present study, we provide in vitro and in vivo evidences that deletion of A20 induces RIPK1 kinase-dependent and -independent apoptosis upon single TNF stimulation. We show that constitutively expressed A20 is recruited to TNFR1 signaling complex (Complex I) via its seventh zinc finger (ZF7) domain, in a cIAP1/2-dependent manner, within minutes after TNF sensing. We demonstrate that Complex I-recruited A20 protects cells from apoptosis by stabilizing the linear (M1) ubiquitin network associated to Complex I, a process independent of its E3 ubiquitin ligase and deubiquitylase (DUB) activities and which is counteracted by the DUB CYLD, both in vitro and in vivo. In absence of linear ubiquitylation, A20 is still recruited to Complex I via its ZF4 and ZF7 domains, but this time protects the cells from death by deploying its DUB activity. Together, our results therefore demonstrate two distinct molecular mechanisms by which constitutively expressed A20 protect cells from TNF-induced apoptosis.

scholarly journals Role of GABA-A and GABA-B receptors of the brain in the hypothalamo-pituitary-testicular regulation by the negative feedback mechanism

1995 ◽  
Vol 41 (4) ◽  
pp. 36-38
Author(s):  
Ye. V. V. Naumenko ◽  
A. V. Amikishiyeva ◽  
L. I. Serova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Negative Feedback ◽  
Feedback Mechanism ◽  
Gaba A ◽  
Negative Feedback Mechanism ◽  
The Central Nervous System ◽  
The Brain ◽  
Stimulation Of

The role of gamma-aminobutyric acid (GABA) of the brain and its receptors in the hypothalamo-pituitary-testicular (HPT) regulation by the negative feedback mechanism was for the first time studied in sham-operated and unilaterally castrated adult Wister rats. Increased level of GABA in the central nervous system following an injection of GABA transaminase inhibitor, aminoacetic acid, into the lateral ventricle of the brain was associated with activation of a compensatory increase of testosterone level in the blood, caused by unilateral castration. GABA effect is mediated through the receptors. Muscimol stimulation of GABA-A receptors of the central nervous system activated and their blocking with bicucullin inhibited a compensatory increase of testosterone level in the blood caused by hemicastration. Baclofen stimulation of cerebral GABA-B receptors was associated with an inhibition and their saclofen blocking with stimulation of the level of male sex steroid hormone in the blood following unilateral castration. A conclusion is made about participation of GABAergic mechanisms of the brain in the regulation of HPT function via the negative feedback mechanism

scholarly journals Maternal starvation primes progeny response to nutritional stress

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009932
Author(s):  
Kelly Voo ◽  
Jeralyn Wen Hui Ching ◽  
Joseph Wee Hao Lim ◽  
Seow Neng Chan ◽  
Amanda Yunn Ee Ng ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Nutritional Stress ◽  
Feedback Mechanism ◽  
Starvation Response ◽  
Pathway Activity ◽  
Tor Pathway ◽  
Negative Feedback Mechanism

Organisms adapt to environmental changes in order to survive. Mothers exposed to nutritional stresses can induce an adaptive response in their offspring. However, the molecular mechanisms behind such inheritable links are not clear. Here we report that in Drosophila, starvation of mothers primes the progeny against subsequent nutritional stress. We found that RpL10Ab represses TOR pathway activity by genetically interacting with TOR pathway components TSC2 and Rheb. In addition, starved mothers produce offspring with lower levels of RpL10Ab in the germline, which results in higher TOR pathway activity, conferring greater resistance to starvation-induced oocyte loss. The RpL10Ab locus encodes for the RpL10Ab mRNA and a stable intronic sequence RNA (sisR-8), which collectively repress RpL10Ab pre-mRNA splicing in a negative feedback mechanism. During starvation, an increase in maternally deposited RpL10Ab and sisR-8 transcripts leads to the reduction of RpL10Ab expression in the offspring. Our study suggests that the maternally deposited RpL10Ab and sisR-8 transcripts trigger a negative feedback loop that mediates intergenerational adaptation to nutritional stress as a starvation response.

scholarly journals Comprehensive Mechanism of Gene Silencing and Its Role in Plant Growth and Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Ahmed H. El-Sappah ◽  
Kuan Yan ◽  
Qiulan Huang ◽  
Md. Monirul Islam ◽  
Quanzi Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plant Growth ◽  
Gene Silencing ◽  
Cell Fate ◽  
Crop Production ◽  
Molecular Mechanisms ◽  
Feedback Mechanism ◽  
Transcriptional Gene Silencing ◽  
Coding Region ◽  
Negative Feedback Mechanism

Gene silencing is a negative feedback mechanism that regulates gene expression to define cell fate and also regulates metabolism and gene expression throughout the life of an organism. In plants, gene silencing occurs via transcriptional gene silencing (TGS) and post-transcriptional gene silencing (PTGS). TGS obscures transcription via the methylation of 5′ untranslated region (5′UTR), whereas PTGS causes the methylation of a coding region to result in transcript degradation. In this review, we summarized the history and molecular mechanisms of gene silencing and underlined its specific role in plant growth and crop production.

Ultrastructural morphology of nontumorous lactotrophs in human pituitaries exposed to high prolactin levels

1987 ◽  
Vol 45 ◽  
pp. 896-897
Author(s):  
S. Jalalah ◽  
K. Kovacs ◽  
E. Horvath
Keyword(s):  
Anterior Pituitary ◽  
Secretory Activity ◽  
Pituitary Hormones ◽  
Feedback Mechanism ◽  
Endocrine Activity ◽  
Hormone Synthesis ◽  
Anterior Pituitary Hormones ◽  
Negative Feedback Mechanism ◽  
Ultrastructural Morphology ◽  
Transmission Electron

Lactotrophs, as many other endocrine cells, change their morphology in response to factors influencing their secretory activity. Secretion of prolactin (PRL) from lactotrophs, like that of other anterior pituitary hormones, is under the control of the hypothalamus. Unlike most anterior pituitary hormones, PRL has no apparent target gland which could modulate the endocrine activity of lactotrophs. It is generally agreed that PRL regulates its own release from lactotrophs via the short loop negative feedback mechanism exerted at the level of the hypothalamus or the pituitary. Accordingly, ultrastructural morphology of lactotrophs is not constant; it is changing in response to high PRL levels showing signs of suppressed hormone synthesis and secretion.By transmission electron microscopy and morphometry, we have studied the morphology of lactotrophs in nontumorous (NT) portions of 7 human pituitaries containing PRL-secreting adenoma; these lactotrophs were exposed to abnormally high PRL levels.

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