scholarly journals Role of Liquid -Liquid Separation in Endocrine and Living cells

2021 ◽  
Author(s):  
Kazuhisa Akiba ◽  
Yuko Katoh-Fukui ◽  
Kei Yoshida ◽  
Satoshi Narumi ◽  
Mami Miyado ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Endocrine Cells ◽  
Evidence Synthesis ◽  
Physical Phenomenon ◽  
Relevant Literature ◽  
Eukaryotic Cell ◽  
Living Cells ◽  
Intrinsically Disordered ◽  
Sex Development

Abstract Context Recent studies have revealed that every eukaryotic cell contains several membraneless organelles created via liquid-liquid phase separation (LLPS). LLPS is a physical phenomenon that transiently compartmentalizes the subcellular space and thereby facilitates various biological reactions. LLPS is indispensable for cellular functions; however, dysregulated LLPS has the potential to cause irreversible protein aggregation leading to degenerative disorders. To date, there is no systematic review on the role of LLPS in endocrinology. Evidence acquisition We explored previous studies which addressed roles of LLPS in living cells, particularly from the viewpoint of endocrinology. To this end, we screened relevant literature in PubMed published between 2009 and 2021 using LLPS-associated keywords including “membraneless organelle”, “phase transition”, and “intrinsically disordered”, and endocrinological keywords such as “hormone”, “ovary”, “androgen”, and “diabetes”. We also referred to the articles in the reference lists of identified papers. Evidence synthesis Based on 67 articles selected from 449 papers, we provided a concise overview of the current understanding of LLPS in living cells. Then, we summarized recent articles documenting the physiological or pathological roles of LLPS in endocrine cells. Conclusions The discovery of LLPS in cells has resulted in a paradigm shift in molecular biology. Recent studies indicate that LLPS contributes to male sex development by providing a functional platform for SOX9 and CBX2 in testicular cells. In addition, dysregulated LLPS has been implicated in aberrant protein aggregation in pancreatic β-cells, leading to type 2 diabetes. Still, we are just beginning to understand the significance of LLPS in endocrine cells.

scholarly journals Impact of porous nanomaterials on inhibiting protein aggregation behaviour

RSC Advances ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 3354-3362
Author(s):  
Munmun Bardhan ◽  
Sandip Dolui ◽  
Siddhi Chaudhuri ◽  
Uttam Paul ◽  
Gaurav Bhattacharjee ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Physiological Conditions ◽  
Intrinsically Disordered ◽  
Aggregation Behaviour ◽  
Inhibiting Protein ◽  
Porous Nanomaterials

Aggregation of intrinsically disordered as well as the ordered proteins under certain premises or physiological conditions leads to pathological disorder.

scholarly journals Backbone assignments, and effect of Asn deamidation, of the N-terminal region of the partitioning protein IncC1 from the plasmid RK2

2021 ◽  
Author(s):  
M. Fayyaz Rehman ◽  
M. Jeeves ◽  
E. I. Hyde
Keyword(s):  
Amino Acids ◽  
Chemical Shift Assignments ◽  
Backbone Assignments ◽  
Intrinsically Disordered ◽  
Nmr Chemical Shift Assignments ◽  
Protein Partner ◽  
Copy Number Plasmid ◽  
Low Copy Number ◽  
Plasmid Rk2

AbstractIncC from the low-copy number plasmid RK2, is a member of the ParA family of proteins required for partitioning DNA in many bacteria and plasmids. It is an ATPase that binds DNA and its ParB protein partner, KorB. Together, the proteins move replicated DNA to appropriate cellular positions, so that each daughter cell inherits a copy on cell division. IncC from RK2 is expressed in two forms. IncC2 is homologous to bacterial ParA proteins, while IncC1 has an N-terminal extension of 105 amino acids and is similar in length to ParA homologues in other plasmids. We have been examining the role of this extension, here called IncC NTD. We present its backbone NMR chemical shift assignments and show that it is entirely intrinsically disordered. The assignments were achieved using C-detected, CON-based spectra, complemented by HNN spectra to obtain connectivities from three adjacent amino acids. We also observed evidence of deamidation of the protein at a GNGG sequence, to give isoAsp, giving 2 sets of peaks for residues up to 5 amino acids on either side of the modification. We have assigned resonances from around the position of modification for this form of the protein.

scholarly journals Connecting the αα-hubs: same fold, disordered ligands, new functions

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lasse Staby ◽  
Katrine Bugge ◽  
Rasmus Greve Falbe-Hansen ◽  
Edoardo Salladini ◽  
Karen Skriver ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Telomere Elongation ◽  
Protein Protein Interaction ◽  
Intrinsically Disordered ◽  
Functional Understanding ◽  
Signal Specificity ◽  
Telomere Regulation ◽  
Secondary Structure Motif

Abstract Background Signal fidelity depends on protein–protein interaction–‘hubs’ integrating cues from large interactomes. Recently, and based on a common secondary structure motif, the αα-hubs were defined, which are small α-helical domains of large, modular proteins binding intrinsically disordered transcriptional regulators. Methods Comparative structural biology. Results We assign the harmonin-homology-domain (HHD, also named the harmonin N-terminal domain, NTD) present in large proteins such as harmonin, whirlin, cerebral cavernous malformation 2, and regulator of telomere elongation 1 to the αα-hubs. The new member of the αα-hubs expands functionality to include scaffolding of supra-modular complexes mediating sensory perception, neurovascular integrity and telomere regulation, and reveal novel features of the αα-hubs. As a common trait, the αα-hubs bind intrinsically disordered ligands of similar properties integrating similar cellular cues, but without cross-talk. Conclusion The inclusion of the HHD in the αα-hubs has uncovered new features, exemplifying the utility of identifying groups of hub domains, whereby discoveries in one member may cross-fertilize discoveries in others. These features make the αα-hubs unique models for decomposing signal specificity and fidelity. Using these as models, together with other suitable hub domain, we may advance the functional understanding of hub proteins and their role in cellular communication and signaling, as well as the role of intrinsically disordered proteins in signaling networks.

scholarly journals A new approach about the digestion of fibers by ruminants

2013 ◽  
Vol 14 (2) ◽  
pp. 382-395 ◽  
Author(s):  
Leonardo Marmo Moreira ◽  
Fernando de Paula Leonel ◽  
Ricardo Augusto Mendonça Vieira ◽  
José Carlos Pereira
Keyword(s):  
Relevant Literature ◽  
Decisive Role ◽  
Supramolecular Systems ◽  
Animal Science ◽  
New Approach ◽  
Feed Resources ◽  
Stable Clusters ◽  
Metallic Cations ◽  
Animal Sciences

The decisive role of metallic cations in the formation of supramolecular clusters involving lignin, cellulose, and hemi-cellulose and its relationship to energy losses in ruminants associated with fibrous feed resources is still not well understood. Indeed, interactions between lignin, cellulose and metallic cations generate highly stable clusters that significantly decrease the capability of cellulase to break bonds between sugar units in order to facilitate the absorption of a great quantity of cellulose, which is ingested by ruminants as forage. Furthermore, several metallic cations cannot be absorbed as a consequence of the formation of coordinated ligations with the oxygen atoms of the lignocellulosic cluster. The loss of lignocellulose-metal clusters by ruminants is responsible for a substantial waste of nutrients, which is a significant problem in animal science. Moreover, the chemical structure of these relevant supramolecular systems is poorly understood. In the present review, we discussed this topic in detail in reference to relevant literature from the chemical and animal sciences in order to analyze the perspectives associated with the improvement of nutritional absorption from feed resources by ruminants.

scholarly journals Regulation of Insulin Secretion and β-Cell Mass by Activating Signal Cointegrator 2

2006 ◽  
Vol 26 (12) ◽  
pp. 4553-4563 ◽  
Author(s):  
Seon-Yong Yeom ◽  
Geun Hyang Kim ◽  
Chan Hee Kim ◽  
Heun Don Jung ◽  
So-Yeon Kim ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Endocrine Cells ◽  
Potential Role ◽  
Cell Mass ◽  
Dominant Negative ◽  
Transcriptional Coactivator ◽  
Β Cells ◽  
Β Cell ◽  
Islet Mass

ABSTRACT Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic β-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/− mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/− mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/− islets. These results suggest that ASC-2 regulates insulin secretion and β-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes.

scholarly journals The New Era of Three-Dimensional Histoarchitecture of the Human Endometrium

2021 ◽  
Vol 11 (8) ◽  
pp. 713
Author(s):  
Manako Yamaguchi ◽  
Kosuke Yoshihara ◽  
Nozomi Yachida ◽  
Kazuaki Suda ◽  
Ryo Tamura ◽  
...  
Keyword(s):  
3D Imaging ◽  
Relevant Literature ◽  
3D Structure ◽  
Three Dimensional ◽  
Human Endometrium ◽  
Tissue Structure ◽  
New Era ◽  
Whole Mount ◽  
Uterine Glands

The histology of the endometrium has traditionally been established by observation of two-dimensional (2D) pathological sections. However, because human endometrial glands exhibit coiling and branching morphology, it is extremely difficult to obtain an entire image of the glands by 2D observation. In recent years, the development of three-dimensional (3D) reconstruction of serial pathological sections by computer and whole-mount imaging technology using tissue clearing methods with high-resolution fluorescence microscopy has enabled us to observe the 3D histoarchitecture of tissues. As a result, 3D imaging has revealed that human endometrial glands form a plexus network in the basalis, similar to the rhizome of grass, whereas mouse uterine glands are single branched tubular glands. This review summarizes the relevant literature on the 3D structure of mouse and human endometrium and discusses the significance of the rhizome structure in the human endometrium and the expected role of understanding the 3D tissue structure in future applications to systems biology.

scholarly journals Validation of a newly developed instrument establishing links between motivation and academic hardiness

2016 ◽  
Vol 12 (1) ◽  
pp. 29-48
Author(s):  
Spiridon Kamtsios ◽  
Evangelia Karagiannopoulou
Keyword(s):  
Elementary School ◽  
School Children ◽  
Elementary School Children ◽  
Convergent Validity ◽  
Factor Model ◽  
Relevant Literature ◽  
Goal Orientations ◽  
Coping Scale ◽  
Academic Hardiness

The purpose of the study was to establish the reliability, the structural and the convergent validity of the “Dimensions of Academic Hardiness Questionnaire” for late elementary school children. A sample of children (N = 1264) aged 10-12 years completed the questionnaire and the “Athens Coping Scale”. Multiple fit indices provided support that the 9-factor model had a good fit to the data. Reliability coefficients ranged from .68 to .83. The study provided also preliminary evidence of convergent validity of the “Dimensions of Academic Hardiness” scores with one theoretically related measure, the “Athens Coping Scale”. The results enrich the notion of Academic Hardiness in late elementary school children as the role of awareness and the role of children’s previous experiences has been distinguished. The relation between the “Dimensions of Academic Hardiness” and achievement goal orientations in children learning is also noted. These findings are discussed in the context of the relevant literature.

Mechanisms and Consequences of Protein Aggregation: The Role of Folding Intermediates

2009 ◽  
Vol 10 (5) ◽  
pp. 456-463 ◽  
Author(s):  
Sangita Seshadri ◽  
Keith Oberg ◽  
Vladimir Uversky
Keyword(s):  
Protein Aggregation ◽  
Folding Intermediates

Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels

2006 ◽  
Vol 291 (4) ◽  
pp. C726-C739 ◽  
Author(s):  
Monica C. Chen ◽  
S. Vincent Wu ◽  
Joseph R. Reeve ◽  
Enrique Rozengurt
Keyword(s):  
Endocrine Cells ◽  
Bitter Taste ◽  
Dependent Manner ◽  
Gi Tract ◽  
Intracellular Ca ◽  
Α Subunits ◽  
Ca2 Channels ◽  
Cck Release

We previously demonstrated the expression of bitter taste receptors of the type 2 family (T2R) and the α-subunits of the G protein gustducin (Gαgust) in the rodent gastrointestinal (GI) tract and in GI endocrine cells. In this study, we characterized mechanisms of Ca2+ fluxes induced by two distinct T2R ligands: denatonium benzoate (DB) and phenylthiocarbamide (PTC), in mouse enteroendocrine cell line STC-1. Both DB and PTC induced a marked increase in intracellular [Ca2+] ([Ca2+]i) in a dose- and time-dependent manner. Chelating extracellular Ca2+ with EGTA blocked the increase in [Ca2+]i induced by either DB or PTC but, in contrast, did not prevent the effect induced by bombesin. Thapsigargin blocked the transient increase in [Ca2+]i induced by bombesin, but did not attenuate the [Ca2+]i increase elicited by DB or PTC. These results indicate that Ca2+ influx mediates the increase in [Ca2+]i induced by DB and PTC in STC-1 cells. Preincubation with the L-type voltage-sensitive Ca2+ channel (L-type VSCC) blockers nitrendipine or diltiazem for 30 min inhibited the increase in [Ca2+]i elicited by DB or PTC. Furthermore, exposure to the L-type VSCCs opener BAY K 8644 potentiated the increase in [Ca2+]i induced by DB and PTC. Stimulation with DB also induced a marked increase in the release of cholecystokinin from STC-1 cells, an effect also abrogated by prior exposure to EGTA or L-type VSCC blockers. Collectively, our results demonstrate that bitter tastants increase [Ca2+]i and cholecystokinin release through Ca2+ influx mediated by the opening of L-type VSCCs in enteroendocrine STC-1 cells.

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