scholarly journals Ca2+-inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM

2021 ◽  
Author(s):  
Ashok Nayak ◽  
Montserrat Samso
Keyword(s):  
Ryanodine Receptor ◽  
Feedback Mechanism ◽  
Salt Bridges ◽  
Negative Feedback Mechanism ◽  
Naturally Occurring ◽  
Subunit Interface ◽  
Ef Hand ◽  
Out Of Plane ◽  
Cytoplasmic Assembly

Activation of the intracellular Ca2+ channel ryanodine receptor (RyR) triggers a cytosolic Ca2+ surge, while elevated cytosolic Ca2+ inhibits the channel in a negative feedback mechanism. Cryo-EM carried out under partially inactivating Ca2+ conditions revealed two conformations of RyR1, an open state and an inactivated state, resolved at 4.0 and 3.3 Angstroms resolution, respectively. RyR1s were embedded in nanodiscs with two lipids resolved at each inter-subunit crevice. Ca2+ binding to the high affinity site engages the central (CD) and C-terminal domains (CTD) into a quasi-rigid unit, which separates the S6 four-helix bundle and opens the channel. Further out-of-plane rotation of the quasi-rigid unit pushes S6 towards the central axis, closing (inactivating) the channel. The inactivated conformation is characterized by a downward conformation of the cytoplasmic assembly, a tightly-knit subunit interface contributed by a fully occupied and partially remodeled Ca2+ activation site, and two salt bridges between the EF hand domain and the S2-S3 loop of the neighboring subunit validated by naturally-occurring disease-causing mutations. Ca2+ also bound to ATP, mediating a tighter interaction between S6 and CTD. Our study suggests that the closed-inactivated is a distinctive state of the RyR1 and its transition to the closed-activable state is not a simple reverse of the Ca2+ mediated activation pathway.

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.

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.

scholarly journals Direct observation of a coil-to-helix contraction triggered by vinculin binding to talin

2020 ◽  
Vol 6 (21) ◽  
pp. eaaz4707 ◽  
Author(s):  
Rafael Tapia-Rojo ◽  
Alvaro Alonso-Caballero ◽  
Julio M. Fernandez
Keyword(s):  
Focal Adhesions ◽  
Interaction Force ◽  
Magnetic Tweezers ◽  
Feedback Mechanism ◽  
Force Transmission ◽  
Mechanical Coupling ◽  
Negative Feedback Mechanism ◽  
The Reformation ◽  
Energy Penalty ◽  
First Time

Vinculin binds unfolded talin domains in focal adhesions, which recruits actin filaments to reinforce the mechanical coupling of this organelle. However, it remains unknown how this interaction is regulated and its impact on the force transmission properties of this mechanotransduction pathway. Here, we use magnetic tweezers to measure the interaction between vinculin head and the talin R3 domain under physiological forces. For the first time, we resolve individual binding events as a short contraction of the unfolded talin polypeptide caused by the reformation of the vinculin-binding site helices, which dictates a biphasic mechanism that regulates this interaction. Force favors vinculin binding by unfolding talin and exposing the vinculin-binding sites; however, the coil-to-helix contraction introduces an energy penalty that increases with force, defining an optimal binding regime. This mechanism implies that the talin-vinculin-actin association could operate as a negative feedback mechanism to stabilize force on focal adhesions.

scholarly journals HOPF BIFURCATION FROM NEW-KEYNESIAN TAYLOR RULE TO RAMSEY OPTIMAL POLICY

2020 ◽  
pp. 1-33
Author(s):  
Jean-Bernard Chatelain ◽  
Kirsten Ralf
Keyword(s):  
Hopf Bifurcation ◽  
Optimal Policy ◽  
Ad Hoc ◽  
Taylor Rule ◽  
Dynamic Properties ◽  
Feedback Mechanism ◽  
New Keynesian ◽  
Negative Feedback Mechanism ◽  
Positive Feedback Mechanism ◽  
Forward Looking

This paper compares different implementations of monetary policy in a new-Keynesian setting. We can show that a shift from Ramsey optimal policy under short-term commitment (based on a negative feedback mechanism) to a Taylor rule (based on a positive feedback mechanism) corresponds to a Hopf bifurcation with opposite policy advice and a change of the dynamic properties. This bifurcation occurs because of the ad hoc assumption that interest rate is a forward-looking variable when policy targets (inflation and output gap) are forward-looking variables in the new-Keynesian theory.

scholarly journals Nitric Oxide-induced Activation of the Type 1 Ryanodine Receptor Is Critical for Epileptic Seizure-induced Neuronal Cell Death

EBioMedicine ◽  
2016 ◽  
Vol 11 ◽  
pp. 253-261 ◽  
Author(s):  
Yoshinori Mikami ◽  
Kazunori Kanemaru ◽  
Yohei Okubo ◽  
Takuya Nakaune ◽  
Junji Suzuki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Ryanodine Receptor ◽  
Epileptic Seizure ◽  
Neuronal Cell Death ◽  
Neuronal Cell

Activation of the Na+/K+-ATPase by insulin and glucose as a putative negative feedback mechanism in pancreatic beta-cells

2008 ◽  
Vol 457 (6) ◽  
pp. 1351-1360 ◽  
Author(s):  
M. Düfer ◽  
D. Haspel ◽  
P. Krippeit-Drews ◽  
L. Aguilar-Bryan ◽  
J. Bryan ◽  
...  
Keyword(s):  
Beta Cells ◽  
Negative Feedback ◽  
Pancreatic Beta Cells ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism

Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia

2000 ◽  
Vol 279 (5) ◽  
pp. H2241-H2248 ◽  
Author(s):  
Hiroshi Saito ◽  
Cam Patterson ◽  
Zhaoyong Hu ◽  
Marschall S. Runge ◽  
Ulka Tipnis ◽  
...  
Keyword(s):  
Feedback Mechanism ◽  
Intercellular Adhesion Molecule ◽  
Regulatory Function ◽  
Heart Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Negative Feedback Mechanism ◽  
Proinflammatory Mediators ◽  
Tnf Α

Interleukin (IL)-6 reportedly has negative inotropic and hypertrophic effects on the heart. Here, we describe endotoxin-induced IL-6 in the heart that has not previously been well characterized. An intraperitoneal injection of a bacterial lipopolysaccharide into C57BL/6 mice induced IL-6 mRNA in the heart more strongly than in any other tissue examined. Induction of mRNA for two proinflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α, occurred rapidly before the induction of IL-6 mRNA and protein. Although stimulation of isolated rat neonatal myocardial cells with IL-1β or TNF-α induced IL-6 mRNA in vitro, nonmyocardial heart cells produced higher levels of IL-6 mRNA upon stimulation with IL-1β. In situ hybridization and immunohistochemical analyses localized the IL-6 expression primarily in nonmyocardial cells in vivo. Endotoxin-induced expression of cardiac IL-1β, TNF-α, and intercellular adhesion molecule 1 was augmented in IL-6-deficient mice compared with control mice. Thus cardiac IL-6, expressed mainly by nonmyocardial cells via IL-1β action during endotoxemia, is likely to suppress expression of proinflammatory mediators and to regulate itself via a negative feedback mechanism.

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.

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