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 Direct Observation of a Coil-to-Helix Contraction Triggered by Vinculin Binding to Talin

2019 ◽  
Author(s):  
Rafael Tapia-Rojo ◽  
Alvaro Alonso-Caballero ◽  
Julio M. Fernandez
Keyword(s):  
Binding Sites ◽  
Focal Adhesions ◽  
Interaction Force ◽  
Magnetic Tweezers ◽  
Feedback Mechanism ◽  
Force Transmission ◽  
Mechanical Coupling ◽  
Negative Feedback Mechanism ◽  
Energy Penalty ◽  
Force Range

Vinculin binds unfolded talin domains in focal adhesions, which recruits actin filaments to rein-force the mechanical coupling of this organelle. However, the mechanism by which this interaction is regulated, and its impact in the force transmission properties of this mechanotransduction pathway remain unknown. Here, we use magnetic tweezers force spectroscopy to measure the binding of vinculin head to the talin R3 domain under physiological force loads. For the first time, we resolve individual binding events as a short contraction of the unfolded talin polypeptide due to the reformation of the helices in the vinculin-binding sites. This force-dependent contraction dictates the mechanism by which force regulates the talin-vinculin interaction. Force is needed to unfold talin and expose the cryptic vinculin-binding sites; however, the structural contraction triggered by binding introduces an energy penalty that increases with force, defining an optimal binding force range. This novel mechanism implies that the talin-vinculin-actin association works in focal adhesions as a negative feedback mechanism, which operates to stabilize the force acting on each junction.

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 Structural and functional analysis of LIM domain-dependent recruitment of paxillin to αvβ3 integrin-positive focal adhesions

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Marta Ripamonti ◽  
Nicolas Liaudet ◽  
Latifeh Azizi ◽  
Daniel Bouvard ◽  
Vesa P. Hytönen ◽  
...  
Keyword(s):  
Focal Adhesions ◽  
Bimolecular Fluorescence Complementation ◽  
Molecular Organization ◽  
Structural Function ◽  
Αvβ3 Integrin ◽  
Lim Domain ◽  
Dissociation Kinetics ◽  
Mechanical Coupling ◽  
Β3 Integrin

AbstractThe LIM domain-dependent localization of the adapter protein paxillin to β3 integrin-positive focal adhesions (FAs) is not mechanistically understood. Here, by combining molecular biology, photoactivation and FA-isolation experiments, we demonstrate specific contributions of each LIM domain of paxillin and reveal multiple paxillin interactions in adhesion-complexes. Mutation of β3 integrin at a putative paxillin binding site (β3VE/YA) leads to rapidly inward-sliding FAs, correlating with actin retrograde flow and enhanced paxillin dissociation kinetics. Induced mechanical coupling of paxillin to β3VE/YA integrin arrests the FA-sliding, thereby disclosing an essential structural function of paxillin for the maturation of β3 integrin/talin clusters. Moreover, bimolecular fluorescence complementation unveils the spatial orientation of the paxillin LIM-array, juxtaposing the positive LIM4 to the plasma membrane and the β3 integrin-tail, while in vitro binding assays point to LIM1 and/or LIM2 interaction with talin-head domain. These data provide structural insights into the molecular organization of β3 integrin-FAs.

On the path toward a universal outflow mechanism in light of NGC 4151 and NGC 1068

2020 ◽  
Vol 15 (S359) ◽  
pp. 283-284
Author(s):  
D. May ◽  
J. E. Steiner ◽  
R. B. Menezes
Keyword(s):  
Near Infrared ◽  
Feedback Mechanism ◽  
Data Cube ◽  
Low Velocity ◽  
Ionized Gas ◽  
Ngc 4151 ◽  
Molecular Outflow ◽  
Ngc 1068 ◽  
Field Unit ◽  
First Time

AbstractWe use near-infrared Integral Field Unit (IFU) data to analyze the galaxies NGC 4151 and NGC 1068, which have very different Eddington ratios - ˜50 times lower for NGC 4151. Together with a detailed data cube treatment methodology, we reveal remarkable similarities between both AGN, such as the detection of the walls of an “hourglass” structure for the low-velocity [Fe ii] emission with the high-velocity emission within this hourglass; a molecular outflow - detected for the first time in NGC 4151; and the fragmentation of an expanding molecular bubble into bullets of ionized gas. Such observations suggest that NGC 4151 could represent a less powerful and more compact version of the outflow seen in NGC 1068, suggesting a universal feedback mechanism acting in quite different AGN.

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.

In silico CDM model sheds light on force transmission in cell from focal adhesions to nucleus

2016 ◽  
Vol 49 (13) ◽  
pp. 2625-2634 ◽  
Author(s):  
Jean-Louis Milan ◽  
Ian Manifacier ◽  
Kevin M. Beussman ◽  
Sangyoon J. Han ◽  
Nathan J. Sniadecki ◽  
...  
Keyword(s):  
In Silico ◽  
Focal Adhesions ◽  
Force Transmission

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

Refusing to Kiss the Slipper

2021 ◽  
Author(s):  
Michael W. Bruening
Keyword(s):  
Religious Authority ◽  
Reform Strategies ◽  
The Reformation ◽  
French Speaking ◽  
Traditional Assumption ◽  
Open Discussion ◽  
First Time ◽  
The Way

Refusing to Kiss the Slipper re-examines the Reformation in francophone Europe, presenting for the first time the perspective of John Calvin’s evangelical enemies. This book brings together a cast of Calvin’s opponents from various French-speaking territories to show that opposition to Calvinism was stronger and better organized than has ever before been recognized. It examines individual opponents, such as Pierre Caroli, Jerome Bolsec, Sebastian Castellio, Charles Du Moulin, and Jean Morély, but more importantly, it explores the anti-Calvinist networks that developed around such individuals. Each group had its own origins and agenda, but all agreed that Calvin’s claim to absolute religious authority too closely echoed the religious sovereignty of the pope. These oft-neglected opponents refused to offer such obeisance—to kiss the papal slipper—arguing instead for open discussion of controversial doctrines. This book also shows that the challenge posed by these groups shaped the way the Calvinists themselves developed their reform strategies. The book demonstrates that the breadth and strength of the anti-Calvinist networks requires us to abandon the traditional assumption that Huguenots and other francophone Protestants were universally Calvinist.

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