scholarly journals Receptor/Raft Ratio Is a Determinant for LRP6 Phosphorylation and WNT/β-Catenin Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Fiete Haack ◽  
Till Köster ◽  
Adelinde M. Uhrmacher
Keyword(s):  
Lipid Rafts ◽  
Protein Complexes ◽  
Vital Role ◽  
Receptor Protein ◽  
Cell Plasma ◽  
Pathway Activation ◽  
Subsequent Activation ◽  
Raft Domains ◽  
First Time ◽  
Specific Membrane

Microdomains or lipid rafts greatly affect the distribution of proteins and peptides in the membrane and play a vital role in the formation and activation of receptor/protein complexes. A prominent example for the decisive impact of lipid rafts on signaling is LRP6, whose localization to the same lipid rafts domain as the kinase CK1γ is crucial for its successful phosphorylation and the subsequent activation of the signalosome, hence WNT/β-catenin signaling. However, according to various experimental measurements, approximately 25 to 35 % of the cell plasma membrane is covered by nanoscopic raft domains with diameters ranging between 10 to 200 nm. Extrapolating/Translating these values to the membrane of a “normal sized” cell yields a raft abundance, that, by far, outnumbers the membrane-associated pathway components of most individual signaling pathway, such as receptor and kinases. To analyze whether and how the quantitative ratio between receptor and rafts affects LRP6 phosphorylation and WNT/β-catenin pathway activation, we present a computational modeling study, that for the first time employs realistic raft numbers in a compartment-based pathway model. Our simulation experiments indicate, that for receptor/raft ratios smaller than 1, i.e., when the number of raft compartments clearly exceeds the number of pathway specific membrane proteins, we observe significant decrease in LRP6 phosphorylation and downstream pathway activity. Our results suggest that pathway specific targeting and sorting mechanism are required to significantly narrow down the receptor/raft ratio and to enable the formation of the LRP6 signalosome, hence signaling.

Caveolin-1, galectin-3 and lipid raft domains in cancer cell signalling

2015 ◽  
Vol 57 ◽  
pp. 189-201 ◽  
Author(s):  
Jay Shankar ◽  
Cecile Boscher ◽  
Ivan R. Nabi
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Cancer Cell ◽  
Cellular Response ◽  
Spatial Organization ◽  
Essential Feature ◽  
Cell Signalling ◽  
Coated Pits ◽  
Signalling Molecules ◽  
Raft Domains

Spatial organization of the plasma membrane is an essential feature of the cellular response to external stimuli. Receptor organization at the cell surface mediates transmission of extracellular stimuli to intracellular signalling molecules and effectors that impact various cellular processes including cell differentiation, metabolism, growth, migration and apoptosis. Membrane domains include morphologically distinct plasma membrane invaginations such as clathrin-coated pits and caveolae, but also less well-defined domains such as lipid rafts and the galectin lattice. In the present chapter, we will discuss interaction between caveolae, lipid rafts and the galectin lattice in the control of cancer cell signalling.

European Mail Armour

2021 ◽  
Author(s):  
Martijn A. Wijnhoven
Keyword(s):  
Early Modern ◽  
Middle Ages ◽  
Iron Age ◽  
Early Modern Period ◽  
Vital Role ◽  
Military Technology ◽  
Roman Army ◽  
Solid Foundation ◽  
First Time

Mail armour (commonly mislabelled 'chainmail') was used for more than two millennia on the battlefield. After its invention in the Iron Age, mail rapidly spread all over Europe and beyond. The Roman army, keen on new military technology, soon adopted mail armour and used it successfully for centuries. Its history did not stop there and mail played a vital role in warfare during the Middle Ages up to the Early Modern Period. Given its long history, one would think mail is a well-documented material, but that is not the case. For the first time, this books lays a solid foundation for the understanding of mail armour and its context through time. It applies a long-term multi-dimensional approach to extract a wealth of as yet untapped information from archaeological, iconographic and written sources. This is complemented with technical insights on the mail maker’s chaîne opératoire.

scholarly journals Acute pain alters P-glycoprotein-containing protein complexes in rat cerebral microvessels: Implications for P-glycoprotein trafficking

2018 ◽  
Vol 38 (12) ◽  
pp. 2209-2222 ◽  
Author(s):  
Margaret E Tome ◽  
Chelsea K Jarvis ◽  
Charles P Schaefer ◽  
Leigh M Jacobs ◽  
Joseph M Herndon ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Protein Complexes ◽  
Activity Increase ◽  
Cerebral Microvessels ◽  
Cns Drug Delivery ◽  
Therapeutic Drugs ◽  
P Glycoprotein ◽  
Cell Plasma ◽  
Rat Paw ◽  
Major Drug

P-glycoprotein (PgP) is the major drug efflux pump in human cerebral microvessels. PgP prevents pathogens, toxins and therapeutic drugs from entering the CNS. Understanding the molecular regulation of PgP activity will suggest novel mechanisms to improve CNS drug delivery. Previously, we found that during peripheral inflammatory pain (PIP) (3 h after λ carrageenan injection in the rat paw), PgP traffics to the cortical microvessel endothelial cell plasma membrane concomitant with increased PgP activity. In the current study, we measured the changes in composition of PgP-containing protein complexes after PIP in rat microvessel isolates. We found that a portion of the PgP is contained in a multi-protein complex that also contains the caveolar proteins CAV1, SDPR, PTRF and PRKCDBP. With PIP, total CAV1 bound to PgP was unchanged; however, phosphorylated CAV1 (Y14P-CAV1) in the complex increased. There were few PgP/CAV1 complexes relative to total PgP and CAV1 in the microvessels suggesting CAV1 bound to PgP is unlikely to affect total PgP activity. However, both PgP and CAV1 trafficked away from the nucleus in response to PIP. These data suggest that P-CAV1 bound to PgP potentially regulates PgP trafficking and contributes to the acute PgP activity increase after a PIP stimulus.

scholarly journals First report on cyanobacterial flora from Masirah Island, Sultanate of Oman

Algologia ◽  
2020 ◽  
Vol 30 (4) ◽  
pp. 440-451
Author(s):  
M. Shamina ◽  
Keyword(s):  
Environmental Conditions ◽  
Food Industry ◽  
Vital Role ◽  
Taxonomic Composition ◽  
Climatic Conditions ◽  
Taxonomic Classification ◽  
Biofuel Production ◽  
Sultanate Of Oman ◽  
First Report ◽  
First Time

Cyanobacteria are organisms which play a vital role in various molecular and biotechnological aspects in food industry, agriculture, pharmaceuticals, neutraceuticals, biofuel production, etc., it is necessary to understand its adaptability to various environmental conditions. Furthermore it is equally important to discover new cyanobacterial taxa and with it occasional changes in taxonomic classification, thus the author set out to study cyanobacteria in extreme climatic conditions of desert, where temperatures are mostly above 45 oC. The taxonomic composition of cyanobacteria of Masirah Island, Sultanate of Oman, was studied for the first time. The studied samples were collected during the period of 2017–2019. The ten samples belonged to two orders: Oscillatoriales Schaffner and Synechococcales L.Hoffmann, Komárek & J.Kastovsky. All of them were filamentous non-heterocyst forms. Three species belonged to the genus Leptolyngbya Anagn. & Komárek, the genera Oscillatoria Vaucher ex Gomont and Lyngbya C.Agardh ex Gomont were represented by two species each, while the genera Pseudanabena Lauterborn, Planktolyngbya Anagn. & Komárek and Geitlerinema (Anagn. & Komárek) Anagn. were one species.

scholarly journals PD-1 Suppresses the Osteogenic and Odontogenic Differentiation of Stem Cells From Dental Apical Papilla via Targeting SHP2/NF-κB axis

2021 ◽  
Author(s):  
Na Li ◽  
Zehan Li ◽  
Lin Fu ◽  
Ming Yan ◽  
Yanqiu Wang ◽  
...  
Keyword(s):  
Vital Role ◽  
Cell Counting ◽  
Alizarin Red ◽  
Odontogenic Differentiation ◽  
Root Dentin ◽  
Apical Papilla ◽  
Effect Of Pd ◽  
First Time ◽  
The Relationship

Abstract BackgroundStem cells from the apical papilla (SCAPs) are important for tooth root development and regeneration of root dentin. Here, we examined the expression of programmed cell death protein-1 (PD-1) in SCAPs and investigated the effect of PD-1 on odontogenic and osteogenic differentiation and the relationship between PD-1 and cell differentiation and SHP2/NF-κB signals.MethodsSCAPs were obtained culture in the related medium. The proliferation ability was evaluated by cell counting kit 8 and 5‐ethynyl‐20‐deoxyuridine (EdU) assay. Alkaline phosphatase (ALP) activity assay, ALP staining, western blot, real-time RT-PCR, Alizarin Red S staining, and immunofluorescence staining were performed to explore the osteo/odontogenic potential and the involvement of SHP2/NF-κB pathways. Besides, we transplanted SCAPs component into mouse calvaria defects to evaluate osteogenesis in vivo. ResultsWe found that human SCAPs expressed PD-1 for the first time. PD-1 knockdown enhanced the osteo/odontogenic differentiation of SCAPs by suppressing SHP2 pathway and activating NF-κB pathway. Overexpression of PD-1 inhibited the osteogenesis and odontogenesis of SCAPs via activation of SHP2 signal and inhibition of NF-κB pathway. ConclusionPD-1 activated SHP2 signal to block NF-κB signal and then played a vital role in osteo/odontogenic differentiation of SCAPs.

scholarly journals Synergistic Assembly of Linker for Activation of T Cells Signaling Protein Complexes in T Cell Plasma Membrane Domains

2003 ◽  
Vol 278 (22) ◽  
pp. 20389-20394 ◽  
Author(s):  
Lorian C. Hartgroves ◽  
Joseph Lin ◽  
Hanno Langen ◽  
Tobias Zech ◽  
Arthur Weiss ◽  
...  
Keyword(s):  
T Cells ◽  
Plasma Membrane ◽  
T Cell ◽  
Protein Complexes ◽  
Membrane Domains ◽  
Cell Plasma Membrane ◽  
Signaling Protein ◽  
Cell Plasma ◽  
Plasma Membrane Domains

Electric features of dislocations and electric force between dislocations

2020 ◽  
pp. 108128652096564
Author(s):  
Yuanjie Huang
Keyword(s):  
Electric Field ◽  
Dielectric Materials ◽  
Dislocation Motion ◽  
Vital Role ◽  
Dislocation Dynamics ◽  
Electric Force ◽  
Fundamental Knowledge ◽  
Large Dielectric Constant ◽  
Net Charges ◽  
First Time

Dislocations and dislocation dynamics are the cores of material plasticity. In this work, the electric features of dislocations were investigated theoretically. An intrinsic electric field around a single dislocation was revealed. In addition to the well-known Peach–Koehler force, it was established that an important intrinsic electric force exists between dislocations, which is uncovered here for the first time and has been neglected since the discovery of dislocations. The electric forces may be large and sometimes could exceed the Peach–Koehler force for metals and some dielectric materials with large dielectric constant. Therefore, the electric force is anticipated to play a vital role in dislocation dynamics and material plasticity. Moreover, an external electric field could exert an electric force on dislocations and a threshold electric field was subsequently discovered above which this force enables dislocations to glide. Interestingly, it was found that some dislocations move in one direction, but others move in reverse in an identical electric field, which is in agreement with experimental observations. Despite dislocation motion under an electric field, to one’s surprise, both edge and screw dislocations do not carry net charges by themselves, which may tackle the long-standing puzzle on the charges of dislocations. These findings may supply people with new fundamental knowledge on dislocations as well as dislocation dynamics, and may assist people in understanding related phenomena.

scholarly journals Single-particle tracking localization microscopy reveals nonaxonemal dynamics of intraflagellar transport proteins at the base of mammalian primary cilia

2019 ◽  
Vol 30 (7) ◽  
pp. 828-837 ◽  
Author(s):  
T. Tony Yang ◽  
Minh Nguyet Thi Tran ◽  
Weng Man Chong ◽  
Chia-En Huang ◽  
Jung-Chi Liao
Keyword(s):  
Particle Tracking ◽  
Single Particle ◽  
Primary Cilia ◽  
Protein Complexes ◽  
Retinal Pigment ◽  
Intraflagellar Transport ◽  
Vital Role ◽  
Single Particle Tracking ◽  
Retinal Pigment Epithelial Cells ◽  
Localization Microscopy

Primary cilia play a vital role in cellular sensing and signaling. An essential component of ciliogenesis is intraflagellar transport (IFT), which is involved in IFT protein recruitment, axonemal engagement of IFT protein complexes, and so on. The mechanistic understanding of these processes at the ciliary base was largely missing, because it is challenging to observe the motion of IFT proteins in this crowded region using conventional microscopy. Here, we report short-trajectory tracking of IFT proteins at the base of mammalian primary cilia by optimizing single-particle tracking photoactivated localization microscopy for IFT88-mEOS4b in live human retinal pigment epithelial cells. Intriguingly, we found that mobile IFT proteins “switched gears” multiple times from the distal appendages (DAPs) to the ciliary compartment (CC), moving slowly in the DAPs, relatively fast in the proximal transition zone (TZ), slowly again in the distal TZ, and then much faster in the CC. They could travel through the space between the DAPs and the axoneme without following DAP structures. We further revealed that BBS2 and IFT88 were highly populated at the distal TZ, a potential assembly site. Together, our live-cell single-particle tracking revealed region-dependent slowdown of IFT proteins at the ciliary base, shedding light on staged control of ciliary homeostasis.

Modular arrangements of sequence motifs determine the functional diversity of KDM proteins

2020 ◽  
Author(s):  
Zerong Wang ◽  
Dongyang Liu ◽  
Baofang Xu ◽  
Ruixia Tian ◽  
Yongchun Zuo
Keyword(s):  
Vital Role ◽  
Sequence Motifs ◽  
Chromatin Dynamics ◽  
Regulatory Motifs ◽  
Demethylase Activity ◽  
Functional Features ◽  
Catalytic Motif ◽  
Functional Mechanisms ◽  
Deep Exploration ◽  
First Time

Abstract Histone lysine demethylases (KDMs) play a vital role in regulating chromatin dynamics and transcription. KDM proteins are given modular activities by its sequence motifs with obvious roles division, which endow the complex and diverse functions. In our review, according to functional features, we classify sequence motifs into four classes: catalytic motifs, targeting motifs, regulatory motifs and potential motifs. JmjC, as the main catalytic motif, combines to Fe2+ and α-ketoglutarate by residues H-D/E-H and S-N-N/Y-K-N/Y-T/S. Targeting motifs make catalytic motifs recognize specific methylated lysines, such as PHD that helps KDM5 to demethylate H3K4me3. Regulatory motifs consist of a functional network. For example, NLS, Ser-rich, TPR and JmjN motifs regulate the nuclear localization. And interactions through the CW-type-C4H2C2-SWIRM are necessary to the demethylase activity of KDM1B. Additionally, many conservative domains that have potential functions but no deep exploration are reviewed for the first time. These conservative domains are usually amino acid-rich regions, which have great research value. The arrangements of four types of sequence motifs generate that KDM proteins diversify toward modular activities and biological functions. Finally, we draw a blueprint of functional mechanisms to discuss the modular activity of KDMs.

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