scholarly journals The dynamic Nexus: Gap junctions control protein localization and mobility in distinct and surprising ways

2020 ◽  
Author(s):  
Sean McCutcheon ◽  
Randy F. Stout ◽  
David C. Spray
Keyword(s):  
Gap Junctions ◽  
Protein Localization ◽  
Second Messengers ◽  
Cellular Interactions ◽  
Dynamic Membrane ◽  
New Information ◽  
Associated Proteins ◽  
Summary Statement ◽  
The Stability ◽  
Membrane Organelle

AbstractGap junction (GJ) channels permit molecules, such as ions, metabolites and second messengers, to transfer between cells. Their function is critical for numerous cellular interactions. GJ channels are composed of Connexin (Cx) hexamers paired across extracellular space and typically form large rafts of clustered channels, called plaques, at cell appositions. Cxs together with molecules that interact with GJ channels make up a supramolecular structure known as the GJ Nexus. While the stability of connexin localization in GJ plaques has been studied, mobility of other Nexus components has yet to be addressed. Colocalization analysis of several nexus components and other membrane proteins reveal that certain molecules are excluded from the GJ plaque (Aquaporin 4, EAAT2b), while others are quite penetrant (lipophilic molecules, Cx30, ZO-1, Occludin). Fluorescence recovery after photobleaching (FRAP) of tagged Nexus-associated proteins showed that mobility in plaque domains is affected by mobility of the Cx proteins. These novel findings indicate that the GJ Nexus is a dynamic membrane organelle, with cytoplasmic and membrane-embedded proteins binding and diffusing according to distinct parameters.Summary StatementGap junctions are clustered membrane channels in plasma membrane of astrocytes and other cells. We report new information on how gap junctions control location and mobility of other astrocyte proteins.

scholarly journals The dynamic Nexus: gap junctions control protein localization and mobility in distinct and surprising ways

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sean McCutcheon ◽  
Randy F. Stout ◽  
David C. Spray
Keyword(s):  
Fluorescence Recovery After Photobleaching ◽  
Protein Localization ◽  
Second Messengers ◽  
Ionic Currents ◽  
Cellular Interactions ◽  
Dynamic Membrane ◽  
Associated Proteins ◽  
The Stability ◽  
Membrane Organelle ◽  
Control Protein

Abstract Gap junction (GJ) channels permit molecules, such as ions, metabolites and second messengers, to transfer between cells. Their function is critical for numerous cellular interactions, providing exchange of metabolites, signaling molecules, and ionic currents. GJ channels are composed of Connexin (Cx) hexamers paired across extracellular space and typically form large rafts of clustered channels, called plaques, at cell appositions. Cxs together with molecules that interact with GJ channels make up a supramolecular structure known as the GJ Nexus. While the stability of connexin localization in GJ plaques has been studied, mobility of other Nexus components has yet to be addressed. Colocalization analysis of several nexus components and other membrane proteins reveal that certain molecules are excluded from the GJ plaque (Aquaporin 4, EAAT2b), while others are quite penetrant (lipophilic molecules, Cx30, ZO-1, Occludin). Fluorescence recovery after photobleaching of tagged Nexus-associated proteins showed that mobility in plaque domains is affected by mobility of the Cx proteins. These novel findings indicate that the GJ Nexus is a dynamic membrane organelle, with cytoplasmic and membrane-embedded proteins binding and diffusing according to distinct parameters.

scholarly journals Phosphoinositides in Retinal Function and Disease

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 866 ◽  
Author(s):  
Theodore G. Wensel
Keyword(s):  
Membrane Trafficking ◽  
New Technologies ◽  
Second Messengers ◽  
Regulatory Pathways ◽  
Peripheral Membrane Proteins ◽  
New Information ◽  
Mammalian Retina ◽  
Pigmented Epithelium ◽  
Associated Proteins ◽  
And Control

Phosphatidylinositol and its phosphorylated derivatives, the phosphoinositides, play many important roles in all eukaryotic cells. These include modulation of physical properties of membranes, activation or inhibition of membrane-associated proteins, recruitment of peripheral membrane proteins that act as effectors, and control of membrane trafficking. They also serve as precursors for important second messengers, inositol (1,4,5) trisphosphate and diacylglycerol. Animal models and human diseases involving defects in phosphoinositide regulatory pathways have revealed their importance for function in the mammalian retina and retinal pigmented epithelium. New technologies for localizing, measuring and genetically manipulating them are revealing new information about their importance for the function and health of the vertebrate retina.

scholarly journals Kinetochores respond to subtle changes in the stability of microtubule attachments

2021 ◽  
Author(s):  
Jessica D. Warren ◽  
Sarah Y. Valles ◽  
Duane A. Compton
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Protein Localization ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Regulatory Enzymes ◽  
Summary Statement ◽  
Spindle Microtubules ◽  
The Stability ◽  
Induced Changes

AbstractProper attachment of spindle microtubules to kinetochores is necessary to satisfy the spindle assembly checkpoint and ensure faithful chromosome segregation. Microtubules detach from kinetochores to correct improperly oriented attachments, and overall kinetochore-microtubule (k-MT) attachment stability is determined in response to regulatory enzymes and the activities of kinetochore-associated microtubule stabilizing and destabilizing proteins. However, it is unknown whether regulatory enzyme activity or kinetochore-associated protein localization respond to subtle changes in k-MT attachment stability. To test for this feedback response, we monitored Aurora B kinase activity and the localization of select kinetochore proteins in metaphase cells following treatments that subtly stabilize or destabilize k-MT attachments using low dose Taxol or UMK57 (an MCAK agonist), respectively. Increasing k-MT stability induced changes in the abundance of some kinetochore proteins. In contrast, reducing k-MT stability induced both increases in Aurora B kinase signaling and changes in the abundance of some kinetochore proteins. Thus, kinetochores dynamically respond to changes in the stability of their attached microtubules. This feedback control contributes to tuning k-MT attachment stability required for efficient error correction to facilitate faithful chromosome segregation.Summary StatementLive cell imaging demonstrates that kinetochore signaling responds to feedback from attached microtubules to tune their stability to ensure faithful chromosome segregation during cell division.

scholarly journals Intercellular calcium signalling between chondrocytes and synovial cells in co-culture

1998 ◽  
Vol 329 (3) ◽  
pp. 681-687 ◽  
Author(s):  
Paola D'ANDREA ◽  
Alessandra CALABRESE ◽  
Micaela GRANDOLFO
Keyword(s):  
Gap Junctions ◽  
Intercellular Communication ◽  
Structural Changes ◽  
Articular Chondrocytes ◽  
Cell Metabolism ◽  
Second Messengers ◽  
Calcium Signalling ◽  
Cell Types ◽  
Synovial Cells ◽  
Cell Coupling

Intercellular communication allows the co-ordination of cell metabolism between tissues as well as sensitivity to extracellular stimuli. Paracrine stimulation and cell-to-cell coupling through gap junctions induce the formation of complex cellular networks that favour the intercellular exchange of nutrients and second messengers. Heterologous intercellular communication was studied in co-cultures of articular chondrocytes and HIG-82 synovial cells by measuring mechanically induced cytosolic changes in Ca2+ ion levels by digital fluorescence video imaging. In confluent co-cultures, mechanical stimulation induced intercellular Ca2+ waves that propagated to both cell types with similar kinetics. Intercellular wave spreading was inhibited by 18α-glycyrrhetinic acid and by treatments inhibiting the activation of purinoreceptors, suggesting that intercellular signalling between these two cell types occurs both through gap junctions and ATP-mediated paracrine stimulation. In rheumatoid arthritis the formation of the synovial pannus induces structural changes at the chondrosynovial junction, where chondrocyte and synovial cells come into close apposition: these results provide the first evidence for direct intercellular communication between these two cell types.

Was the Bank Holiday of 1933 Caused by a Run on the Dollar?

1987 ◽  
Vol 47 (3) ◽  
pp. 739-755 ◽  
Author(s):  
Barrie A. Wigmore
Keyword(s):  
New York ◽  
Foreign Exchange ◽  
Federal Reserve ◽  
Deposit Insurance ◽  
Banking System ◽  
Domestic Currency ◽  
New Information ◽  
The Stability ◽  
Specific Timing

International, rather than domestic, causes of both the Bank Holiday of 1933 and the calm in the banking system that followed are emphasized here. New information on gold losses by the New York Federal Reserve, rather than domestic currency hoarding, serve to explain the Bank Holiday's specific timing. Expectations that Roosevelt would devalue the dollar stimulated much of the gold loss. I also argue that Roosevelt's restrictions on gold holdings and foreign exchange dealings and his devaluation of the dollar by 60 percent were more important to the stability of the banking system after the Bank Holiday than was deposit insurance.

scholarly journals The Putative RNA-Binding Protein Nrp1 Promotes the Loading of Kinesin-14/Klp2 to the Mitotic Spindle and Is Sequestered Into Heat-Induced Protein Aggregates in Fission Yeast

2021 ◽  
Author(s):  
Masashi Yukawa ◽  
Mitsuki Ohishi ◽  
Yusuke Yamada ◽  
Takashi Toda
Keyword(s):  
Fission Yeast ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Aggregates ◽  
Associated Proteins ◽  
Spindle Microtubules ◽  
The Stability ◽  
And Function ◽  
Post Transcriptional Regulation

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper spindle architecture is established by a set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 motors are essential for this process, and genetic or chemical inhibition of their activity leads to the emergence of monopolar spindles and cell death. However, these deficiencies can be rescued by simultaneous inactivation of kinesin-14 motors, as they counteract kinesin-5. We conducted detailed genetic analyses in fission yeast to understand the mechanisms driving spindle assembly in the absence of kinesin-5. Here we show that deletion of the nrp1 gene, which encodes a putative RNA-binding protein with unknown function, can rescue temperature sensitivity caused by cut7-22, a fission yeast kinesin-5 mutant. Interestingly, kinesin-14/Klp2 levels on the spindles in the cut7 mutants were significantly reduced by the nrp1 deletion, although the total levels of Klp2 and the stability of spindle microtubules remained unaffected. Moreover, RNA-binding motifs of Nrp1 are essential for its cytoplasmic localization and function. We have also found that a portion of Nrp1 is spatially and functionally sequestered by chaperone-based protein aggregates upon mild heat stress and limits cell division at high temperatures. We propose that Nrp1 might be involved in post-transcriptional regulation through its RNA-binding ability to promote the loading of Klp2 on the spindle microtubules.

The phylogenetic relationships of the two-winged South American Leptophlebiidae genera revisited with first description of the male imago of Bessierus Thomas & Orth (Insecta: Ephemeroptera)

Zootaxa ◽  
2019 ◽  
Vol 4674 (3) ◽  
pp. 375-385
Author(s):  
EDUARDO DOMÍNGUEZ ◽  
MARÍA GABRIELA CUEZZO ◽  
SIMÓN CLAVIER
Keyword(s):  
Sister Group ◽  
Sister Group Relationship ◽  
South American ◽  
Phylogenetic Hypothesis ◽  
New Information ◽  
Statistical Support ◽  
The Stability ◽  
New Diagnosis ◽  
Relationship Of ◽  
First Time

Four of the 43 genera of South American Leptophlebiidae are dipterous. A previous phylogenetic hypothesis supported that clade Askola+Hagenulopsis, and that Bessierus+Perissophlebiodes, are sister groups of the Farrodes complex. Adults of Bessierus and Perissophlebiodes were not known but posteriorly Perissophlebiodes male imago was described. Here, we describe the male imago of Bessierus for the first time. Both genera share, besides the absence of the hind wings, the asymmetrical fork of MA, symmetrical fork of MP, dissimilar tarsal claws, and forceps sockets fused. Along with the description of the imago, a new diagnosis for the genus Bessierus is presented, also updating the identification key with this new information. A new cladistics analysis is performed to test the stability of the proposed relationships of these four genera within Leptophlebiidae. We obtained a single cladistic hypothesis where the addition of Bessierus adult characters resulted in new synapomorphies for the (Bessierus, Perissophlebiodes) clade, and improved its clade statistical support. The fused forceps sockets resulted in a synapomorphy uniting Bessierus, Perissophlebiodes and Simothraulopsis. As a result of this new analysis, the hypothesis of independent losses of the hind wings in the two dipterous groups studied is supported. The Farrodes lineage is not supported as proposed in previous studies, being restricted only to (Farrodes (Simothraulopsis, Homothraulus)) while the identity of “Perissophlebiodes lineage” is supported. The sister group relationship of Rondophlebia is not clearly defined. 

Model Mediated Telemanipulation

2006 ◽  
Author(s):  
Probal Mitra ◽  
Gu¨nter Niemeyer
Keyword(s):  
Force Feedback ◽  
Sensory Information ◽  
Virtual Model ◽  
Basic Principles ◽  
Natural Motion ◽  
New Information ◽  
Remote Environment ◽  
The Stability ◽  
Master Device

A telemanipulation system allows a human user to manipulate a remote environment using a local interface (master robot) to control a remote (slave) robot. In doing so, it is desirable to provide users with appropriate sensory feedback, most often taking the form of visual and force information. In the presence of communication delays, however, a force feedback telemanipulation system must overcome detrimental effects caused by the delay, both on the quality of feedback to the user and the stability of the control system. For large delays, like those experienced in space telerobotics, the user's perceptive abilities are distorted and challenged by the lag between action and response. With this paper, a user-centered approach is proposed which seeks to simultaneously provide stable master-slave interaction as well as a natural user experience, tolerant of large delays. Rather than directly sending sensory information from the slave robot to the user, the goal is to use this information to create a real-time virtual model of the remote environment, which then serves as the user's interface. Maintaining a dynamic, virtual model locally at the master-side, the user is provided with immediate visual and haptic responses to his/her actions through the master device. At the remote site, the slave robot tracks the user's continuous and natural motion commands, while providing new information needed to update the virtual model. This method abstracts the data transmitted between the sites and creates greater delay tolerance. The basic principles of the approach are demonstrated on a simple one-degree of freedom telerobotic system, with a rigid, stationary slave environment.

Identification of second messengers that induce expression of functional gap junctions in microglia cultured from newborn rats

2002 ◽  
Vol 943 (2) ◽  
pp. 191-201 ◽  
Author(s):  
Agustı́n D Martı́nez ◽  
Eliseo A Eugenı́n ◽  
Marı́a C Brañes ◽  
Michael V.L Bennett ◽  
Juan C Sáez
Keyword(s):  
Gap Junctions ◽  
Second Messengers ◽  
Newborn Rats

scholarly journals Gap junctions and connexin hemichannels in the regulation of haemostasis and thrombosis

2015 ◽  
Vol 43 (3) ◽  
pp. 489-494 ◽  
Author(s):  
Sakthivel Vaiyapuri ◽  
Gagan D. Flora ◽  
Jonathan M. Gibbins
Keyword(s):  
Gap Junctions ◽  
Intercellular Communication ◽  
Heart Attack ◽  
Wound Repair ◽  
Future Directions ◽  
Tissue Responses ◽  
The Stability ◽  
And Control ◽  
Connexin Hemichannels

Platelets are involved in the maintenance of haemostasis but their inappropriate activation leads to thrombosis, a principal trigger for heart attack and ischaemic stroke. Although platelets circulate in isolation, upon activation they accumulate or aggregate together to form a thrombus, where they function in a co-ordinated manner to prevent loss of blood and control wound repair. Previous report (1) indicates that the stability and functions of a thrombus are maintained through sustained, contact-dependent signalling between platelets. Given the role of gap junctions in the co-ordination of tissue responses, it was hypothesized that gap junctions may be present within a thrombus and mediate intercellular communication between platelets. Therefore studies were performed to explore the presence and functions of connexins in platelets. In this brief review, the roles of hemichannels and gap junctions in the control of thrombosis and haemostasis and the future directions for this research will be discussed.

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