scholarly journals Mechanical stretch regulates macropinocytosis in Hydra vulgaris

2021 ◽  
Author(s):  
Taylor D. Skokan ◽  
Bert Hobmayer ◽  
Kara L. McKinley ◽  
Ronald D. Vale
Keyword(s):  
Large Scale ◽  
Calcium Influx ◽  
Mechanical Stretch ◽  
Entire Body ◽  
Membrane Tension ◽  
Hydra Vulgaris ◽  
Culture Models ◽  
Simple Body ◽  
Molecular Machinery ◽  
Stretch Activated Channels

AbstractCells rely on a diverse array of engulfment processes to sense, exploit, and adapt to their environments. Macropinocytosis is a versatile example of such a process, allowing for the indiscriminate and rapid uptake of large volumes of fluid and membrane. Much of the molecular machinery essential for macropinocytosis has been well established. However, most of these studies relied on tissue culture models, leaving the regulation of this process within the context of organs and organisms unresolved. Here, we report that large-scale macropinocytosis occurs in the outer epithelial layer of the cnidarian Hydra vulgaris. Exploiting Hydra’s relatively simple body plan, we developed approaches to visualize macropinocytosis over extended periods of time in living tissue, revealing constitutive engulfment across the entire body axis. Using pharmacological perturbations, we establish a role for stretch-activated channels, including Piezo, and downstream calcium influx in inhibiting this process. Finally, we show that the direct application of planar stretch leads to calcium influx and a corresponding inhibition of macropinocytosis. Together, our approaches provide a platform for the mechanistic dissection of constitutive macropinocytosis in physiological contexts and reveal a role for macropinocytosis in responding to membrane tension.

scholarly journals Business rules specification and business processes modeling

2009 ◽  
Vol 55 (No. 1) ◽  
pp. 20-24 ◽  
Author(s):  
I. Rábová
Keyword(s):  
Process Model ◽  
Large Scale ◽  
Business Processes ◽  
System Development ◽  
Entire Body ◽  
Business Rules ◽  
Business Rule ◽  
Policy Document ◽  
Business Policy ◽  
Body Of Knowledge

Up to date business is managed by large-scale different rules that regulate how the business acts and how it is structured. We find the rules in law, regulation, business policy document, procedures manual, system documentation, memoranda etc. These reference resources may provide the specific basis for a rule or offer a background, context or explanation of the business rule. In the recent years, it has been discovered that business rules constitute an entire body of knowledge that has not been adequately addressed in either the analysis or design phases of the information system development. Typically, business rules have been buried in the program code or in the database structures. The article deals with the business rules approach and rule technology and helps to identify the business and technical opportunities they afford to the company. It offers the business process model and its integration with business rules. This approach could provide business analysts with an essential approach to understanding, redesigning and communicating what really happens in the business processes (in agricultural area). It serves to understand the business impact of any change in small and medium-sized organizations. We use the UML notation and its business model extension.

Ca2+ uptake in GH3 cells during hypotonic swelling: the sensory role of stretch-activated ion channels

1996 ◽  
Vol 270 (6) ◽  
pp. C1790-C1798 ◽  
Author(s):  
Y. Chen ◽  
S. M. Simasko ◽  
J. Niggel ◽  
W. J. Sigurdson ◽  
F. Sachs
Keyword(s):  
Volume Regulation ◽  
Cell Swelling ◽  
Gh3 Cells ◽  
Membrane Tension ◽  
Hypotonic Cell Swelling ◽  
Stretch Activated Channels ◽  
Ca2 Channels ◽  
Hypotonic Swelling ◽  
Volume Decrease

Hypotonic cell swelling triggers an increase in intracellular Ca2+ concentration that is deemed responsible for the subsequent regulated volume decrease in many cells. To understand the mechanisms underlying this increase, we have studied the Ca2+ sources that contribute to hypotonic cell swelling-induced Ca2+ increase (HICI) in GH3 cells. Fura 2 fluorescence of cell populations revealed that extracellular, but not intracellular, stores of Ca2+ were required. HICI was abolished by nifedipine, a blocker of L-type Ca2+ channels, and Gd3+, a nonspecific blocker of stretch-activated channels (SACs), suggesting two components for the Ca2+ membrane pathway: L-type Ca2+ channels and SACs. Using HICI as an assay, we found that venom from the spider Grammostola spatulata could block HICI without blocking L-type Ca2+ channels. The venom did, however, block SAC activity. This suggests that Ca(2+)-permeable SACs, rather than L-type Ca2+ channels, are the sensing elements for HICI. These results support the model for volume regulation in which SACs, activated by an increase of the membrane tension during hypotonic cell swelling, trigger HICI, leading to a volume decrease.

Calcium influx through stretch-activated channels mediates microfilament reorganization in osteoblasts under simulated weightlessness

2013 ◽  
Vol 51 (11) ◽  
pp. 2058-2068 ◽  
Author(s):  
Mingzhi Luo ◽  
Zhouqi Yang ◽  
Jingbao Li ◽  
Huiyun Xu ◽  
Shengsheng Li ◽  
...  
Keyword(s):  
Calcium Influx ◽  
Simulated Weightlessness ◽  
Stretch Activated Channels

Mechanical stretch/relaxation of cultured rat mesangial cells induces protooncogenes and cyclooxygenase

1994 ◽  
Vol 267 (2) ◽  
pp. C482-C490 ◽  
Author(s):  
Y. Akai ◽  
T. Homma ◽  
K. D. Burns ◽  
T. Yasuda ◽  
K. F. Badr ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mesangial Cells ◽  
Calcium Influx ◽  
Regulation Of Gene Expression ◽  
Calcium Content ◽  
Mechanical Stretch ◽  
Glomerular Mesangial Cells ◽  
Cell Functions ◽  
Kinase C

In cultured rat glomerular mesangial cells, continuous cycles of stretching and relaxation (stretch/relaxation) stimulate cell proliferation, protein synthesis, and prostaglandin production. We examined regulation of gene expression that may underlie these alterations in cell functions. Stretch/relaxation caused time-dependent induction of the immediate early genes, c-fos and zif 268/egr-1, with maximal increases occurring between 15 and 30 min. The mitogen-inducible prostaglandin G2/H2 synthase (PGH2S-2) gene was also induced within 30 min of stretch/relaxation, with concomitant increases in the immunoreactive PGH2S-2 protein. These gene inductions were preceded by transient translocation of protein kinase C activity from cytosol to membrane as well as by increases in 45Ca2+ uptake and total cellular calcium content. The stretch/relaxation-induced expression was suppressed by protein kinase C inhibition, whereas less profound inhibition was observed with inhibition of calcium influx in low (100 nM) calcium buffer. These findings indicate that in mesangial cells mechanical stress induces expression of the protooncogenes and the mitogen-inducible cyclooxygenase primarily through protein kinase C-dependent mechanisms.

scholarly journals Mechanical Stretch Kills Transformed Cancer Cells

2018 ◽  
Author(s):  
Ajay Tijore ◽  
Mingxi Yao ◽  
Yu-Hsiu Wang ◽  
Yasaman Nematbakhsh ◽  
Anushya Hariharan ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Calcium Influx ◽  
Mechanical Stretch ◽  
Cyclic Stretch ◽  
Transformed Cells ◽  
Normal Cells ◽  
Calcium Dependent ◽  
Cyclic Stretching ◽  
Protease Activation ◽  
Different Tissues

AbstractTransformed cancer cells differ from normal cells in several important features like anchorage independence, Warburg effect and mechanosensing. Consequently, transformed cancer cells develop an anaplastic morphology and respond aberrantly to external mechanical forces. Consistent with altered mechano-responsiveness, here we show that transformed cancer cells from many different tissues have reduced growth and become apoptotic upon cyclic stretch as do normal cells after the transformation. When matrix rigidity sensing is restored in transformed cancer cells, they survive and grow faster on soft surface upon cyclic stretch like normal cells but undergo anoikis without stretch by activation of death associated protein kinase1 (DAPK1). In contrast, stretch-dependent apoptosis (mechanoptosis) of transformed cells is driven by stretch-mediated calcium influx and calcium-dependent calpain 2 protease activation on both collagen and fibronectin matrices. Further, mechanosensitive calcium channel, Piezo1 is needed for mechanoptosis. Thus, cyclic stretching of transformed cells from different tissues activates apoptosis, whereas similar stretching of normal cells stimulates growth.

scholarly journals Biochemical computation underlying behavioral decision-making

2020 ◽  
Author(s):  
Stephen C. Thornquist ◽  
Maximilian J. Pitsch ◽  
Charlotte S. Auth ◽  
Michael A. Crickmore
Keyword(s):  
Large Scale ◽  
Calcium Influx ◽  
Recurrent Network ◽  
Biochemical Activity ◽  
Measuring Time ◽  
Elapsed Time ◽  
Behavioral Decision ◽  
Internal Measurement ◽  
Long Timescales ◽  
The Brain

AbstractComputations in the brain are broadly assumed to emerge from patterns of fast electrical activity. Challenging this view, we show that a male fly’s decision to persist in mating, even through a potentially lethal threat, hinges on biochemical computations that enable processing over minutes to hours. Each neuron in a recurrent network measuring time into mating contains slightly different internal molecular estimates of elapsed time. Protein Kinase A (PKA) activity contrasts this internal measurement with input from the other neurons to represent evidence that the network’s goal has been achieved. When consensus is reached, PKA pushes the network toward a large-scale and synchronized burst of calcium influx, which we call an eruption. The eruption functions like an action potential at the level of the network, transforming deliberation within the network into an all-or-nothing output, after which the male will no longer sacrifice his life to continue mating. We detail the continuous transformation between interwoven molecular and electrical information over long timescales in this system, showing how biochemical activity, invisible to most large scale recording techniques, is the key computational currency directing a life-or-death decision.

scholarly journals Piezo1 links mechanical forces to red blood cell volume

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Stuart M Cahalan ◽  
Viktor Lukacs ◽  
Sanjeev S Ranade ◽  
Shu Chien ◽  
Michael Bandell ◽  
...  
Keyword(s):  
Blood Cell ◽  
Calcium Influx ◽  
Mechanical Stretch ◽  
Conditional Knockout ◽  
Volume Control ◽  
Mechanical Forces ◽  
Gardos Channel

Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis.

scholarly journals Simulations of Myenteric Neuron Dynamics in Response to Mechanical Stretch

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Donghua Liao ◽  
Jingbo Zhao ◽  
Hans Gregersen
Keyword(s):  
Large Scale ◽  
Visceral Pain ◽  
Mechanical Stretch ◽  
Compartment Model ◽  
Building Blocks ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Myenteric Neuron ◽  
Mechanoelectrical Transduction ◽  
Physiological Outcomes

Background. Intestinal sensitivity to mechanical stimuli has been studied intensively in visceral pain studies. The ability to sense different stimuli in the gut and translate these to physiological outcomes relies on the mechanosensory and transductive capacity of intrinsic intestinal nerves. However, the nature of the mechanosensitive channels and principal mechanical stimulus for mechanosensitive receptors are unknown. To be able to characterize intestinal mechanoelectrical transduction, that is, the molecular basis of mechanosensation, comprehensive mathematical models to predict responses of the sensory neurons to controlled mechanical stimuli are needed. This study aims to develop a biophysically based mathematical model of the myenteric neuron with the parameters constrained by learning from existing experimental data. Findings. The conductance-based single-compartment model was selected. The parameters in the model were optimized by using a combination of hand tuning and automated estimation. Using the optimized parameters, the model successfully predicted the electrophysiological features of the myenteric neurons with and without mechanical stimulation. Conclusions. The model provides a method to predict features and levels of detail of the underlying physiological system in generating myenteric neuron responses. The model could be used as building blocks in future large-scale network simulations of intrinsic primary afferent neurons and their network.

scholarly journals Involvement of KCaChannels and Stretch-Activated Channels in Calcium Influx, Triggering Membrane Fusion of Chick Embryonic Myoblasts

1996 ◽  
Vol 175 (1) ◽  
pp. 14-23 ◽  
Author(s):  
Ki Soon Shin ◽  
Jae Yong Park ◽  
Doo Bong Ha ◽  
Chin Ha Chung ◽  
Man-Sik Kang
Keyword(s):  
Membrane Fusion ◽  
Calcium Influx ◽  
Stretch Activated Channels

scholarly journals Identifying and characterizing a novel Sindbis virus capsid and IRAK1 interaction

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
V Landers ◽  
Kevin Sokoloski
Keyword(s):  
Capsid Protein ◽  
Genome Stability ◽  
Sindbis Virus ◽  
Large Scale ◽  
Severe Disease ◽  
Bimolecular Fluorescence Complementation ◽  
Tlr Agonist ◽  
Culture Models ◽  
Host Innate Immune Response ◽  
Rna Stabilization

Alphaviruses are arthropod-borne positive-sense RNA viruses that have the capacity to cause large scale outbreaks of severe disease. As of now, there are no effective therapeutic strategies with which alphaviral disease may be treated. Thus, there is a need for research that defines the mechanism(s) by which the alphaviruses establish infection and cause pathogenesis. Our previous work identified non-assembly interactions between the SINV Capsid protein and the viral genomic RNA that were important for viral RNA stabilization early during infection. These efforts led us to evaluate the Protein:Protein interactions of the SINV Capsid protein using the BioID2 discovery approach to define the mechanism of action underlying the SINV Capsid-mediated genome stability. To our surprise, these efforts indicated that the SINV CP protein interacts with the host IRAK1 protein in tissue culture models of infection. To validate the interface we utilized a Bimolecular Fluorescence Complementation approach to confirm the SINV Capsid-IRAK1 interaction. After confirming the novel Capsid Protein:Protein interaction we hypothesized that the SINV Capsid protein may interfere with IRAK1-dependent signaling during infection. To this end, we assessed the dose-responsiveness of several IRAK1-dependent signaling pathways, including TLRs 4 and 7 in the presence of the SINV Capsid protein. We found that the TLR-agonist response, was significantly decreased in the presence of the SINV Capsid protein. Collectively, these data are highly suggestive that the SINV Capsid protein interferes with TLR signaling during viral infection contributing to the evasion of the host innate immune response.

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