scholarly journals Activity and Function of the PRMT8 Protein Arginine Methyltransferase in Neurons

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1132
Author(s):  
Rui Dong ◽  
Xuejun Li ◽  
Kwok-On Lai
Keyword(s):  
Potential Role ◽  
Neurological Diseases ◽  
Structural Features ◽  
Protein Arginine Methyltransferases ◽  
Synapse Maturation ◽  
Membrane Bound ◽  
And Function ◽  
Neuronal Functions ◽  
Mammalian Protein

Among the nine mammalian protein arginine methyltransferases (PRMTs), PRMT8 is unusual because it has restricted expression in the nervous system and is the only membrane-bound PRMT. Emerging studies have demonstrated that this enzyme plays multifaceted roles in diverse processes in neurons. Here we will summarize the unique structural features of PRMT8 and describe how it participates in various neuronal functions such as dendritic growth, synapse maturation, and synaptic plasticity. Recent evidence suggesting the potential role of PRMT8 function in neurological diseases will also be discussed.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

scholarly journals Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels

2021 ◽  
Vol 14 ◽  
Author(s):  
Deepanjali Dwivedi ◽  
Upinder S. Bhalla
Keyword(s):  
Ion Channels ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Brain Regions ◽  
Channel Activity ◽  
Current Review ◽  
Cellular Excitability ◽  
M Channels ◽  
Neuronal Functions

SK, HCN, and M channels are medium afterhyperpolarization (mAHP)-mediating ion channels. The three channels co-express in various brain regions, and their collective action strongly influences cellular excitability. However, significant diversity exists in the expression of channel isoforms in distinct brain regions and various subcellular compartments, which contributes to an equally diverse set of specific neuronal functions. The current review emphasizes the collective behavior of the three classes of mAHP channels and discusses how these channels function together although they play specialized roles. We discuss the biophysical properties of these channels, signaling pathways that influence the activity of the three mAHP channels, various chemical modulators that alter channel activity and their therapeutic potential in treating various neurological anomalies. Additionally, we discuss the role of mAHP channels in the pathophysiology of various neurological diseases and how their modulation can alleviate some of the symptoms.

scholarly journals Role of the PDZ Domains in Escherichia coli DegP Protein

2007 ◽  
Vol 189 (8) ◽  
pp. 3176-3186 ◽  
Author(s):  
Jack Iwanczyk ◽  
Daniela Damjanovic ◽  
Joel Kooistra ◽  
Vivian Leong ◽  
Ahmad Jomaa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Protease Activity ◽  
Pdz Domain ◽  
Structural Features ◽  
Periplasmic Protein ◽  
Pdz Domains ◽  
Protease Domain ◽  
Interaction Domains ◽  
And Function

ABSTRACT PDZ domains are modular protein interaction domains that are present in metazoans and bacteria. These domains possess unique structural features that allow them to interact with the C-terminal residues of their ligands. The Escherichia coli essential periplasmic protein DegP contains two PDZ domains attached to the C-terminal end of the protease domain. In this study we examined the role of each PDZ domain in the protease and chaperone activities of this protein. Specifically, DegP mutants with either one or both PDZ domains deleted were generated and tested to determine their protease and chaperone activities, as well as their abilities to sequester unfolded substrates. We found that the PDZ domains in DegP have different roles; the PDZ1 domain is essential for protease activity and is responsible for recognizing and sequestering unfolded substrates through C-terminal tags, whereas the PDZ2 domain is mostly involved in maintaining the hexameric cage of DegP. Interestingly, neither of the PDZ domains was required for the chaperone activity of DegP. In addition, we found that the loops connecting the protease domain to PDZ1 and connecting PDZ1 to PDZ2 are also essential for the protease activity of the hexameric DegP protein. New insights into the roles of the PDZ domains in the structure and function of DegP are provided. These results imply that DegP recognizes substrate molecules targeted for degradation and substrate molecules targeted for refolding in different manners and suggest that the substrate recognition mechanisms may play a role in the protease-chaperone switch, dictating whether the substrate is degraded or refolded.

Stem Cells from Human Exfoliated Deciduous Teeth and their Promise as Preventive and Therapeutic Strategies for Neurological Diseases and Injuries

2021 ◽  
Vol 17 ◽  
Author(s):  
Lingyi Huang ◽  
Zizhuo Zheng ◽  
Ding Bai ◽  
Xianglong Han
Keyword(s):  
Stem Cells ◽  
Potential Role ◽  
Neurological Diseases ◽  
Therapeutic Strategies ◽  
Deciduous Teeth ◽  
Research Attention ◽  
Considerable Potential ◽  
Prevention And Treatment ◽  
Human Exfoliated Deciduous Teeth

Abstract: Stem cells from human exfoliated deciduous teeth (SHEDs) are relatively easy to isolate from exfoliated deciduous teeth, which are obtained via dental therapy as biological waste. SHEDs originate from the embryonic neural crest and therefore have considerable potential for neurogenic differentiation. Currently, an increasing amount of research attention is focused on the therapeutic applications of SHEDs in neurological diseases and injuries. In this article, we summarize the biological characteristics of SHEDs and the potential role of SHEDs and their derivatives, including conditioned medium from SHEDs and the exosomes they secrete, in the prevention and treatment of neurological diseases and injuries.

scholarly journals Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Kavita Singh ◽  
Martin Burkhardt ◽  
Sofia Nakuchima ◽  
Raul Herrera ◽  
Olga Muratova ◽  
...  
Keyword(s):  
Membrane Surface ◽  
Structure And Function ◽  
Fab Fragment ◽  
Membrane Anchor ◽  
Transmission Blocking ◽  
Vaccine Candidates ◽  
Membrane Bound ◽  
And Function ◽  
Transmission Blocking Vaccine

AbstractProteins Pfs230 and Pfs48/45 are Plasmodium falciparum transmission-blocking (TB) vaccine candidates that form a membrane-bound protein complex on gametes. The biological role of Pfs230 or the Pfs230-Pfs48/45 complex remains poorly understood. Here, we present the crystal structure of recombinant Pfs230 domain 1 (Pfs230D1M), a 6-cysteine domain, in complex with the Fab fragment of a TB monoclonal antibody (mAb) 4F12. We observed the arrangement of Pfs230 on the surface of macrogametes differed from that on microgametes, and that Pfs230, with no known membrane anchor, may exist on the membrane surface in the absence of Pfs48/45. 4F12 appears to sterically interfere with Pfs230 function. Combining mAbs against different epitopes of Pfs230D1 or of Pfs230D1 and Pfs48/45, significantly increased TB activity. These studies elucidate a mechanism of action of the Pfs230D1 vaccine, model the functional activity induced by a polyclonal antibody response and support the development of TB vaccines targeting Pfs230D1 and Pfs230D1-Pfs48/45.

scholarly journals Metabolomic Identification of Exosome-Derived Biomarkers for Schizophrenia: A Large Multicenter Study

2020 ◽  
Author(s):  
Yang Du ◽  
Lei Chen ◽  
Xue-Song Li ◽  
Xiao-Lin Li ◽  
Xiang-Dong Xu ◽  
...  
Keyword(s):  
Potential Role ◽  
Neurological Diseases ◽  
Bioinformatic Analysis ◽  
Ultra Performance Liquid Chromatography ◽  
Training Samples ◽  
Liquid Chromatography Tandem Mass ◽  
Test Sets ◽  
And Control ◽  
Metabolomic Study

Abstract Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.

scholarly journals Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

2020 ◽  
Vol 9 (10) ◽  
pp. 3296
Author(s):  
Aeman Zahra ◽  
Cristina Sisu ◽  
Elisabete Silva ◽  
Sophie-Christine De Aguiar Greca ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Angiotensin Converting Enzyme 2 ◽  
Endocrine Disrupting ◽  
Membrane Bound ◽  
Transmembrane Serine Protease ◽  
G Protein Coupled

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

scholarly journals Endocrine Significance of SARS-CoV-2’s Reliance on ACE2

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Eric Lazartigues ◽  
Mirza Muhammad Fahd Qadir ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Potential Role ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Impact ◽  
The Past ◽  
And Function ◽  
Endocrine Tissues

Abstract The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.

scholarly journals Perspectives on the Role of Non-Coding RNAs in the Regulation of Expression and Function of the Estrogen Receptor

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2162
Author(s):  
Mohammad Taheri ◽  
Hamed Shoorei ◽  
Marcel E. Dinger ◽  
Soudeh Ghafouri-Fard
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Reproductive System ◽  
Estrogen Regulation ◽  
Tissue Specific ◽  
Membrane Bound ◽  
Non Coding Rnas ◽  
And Function ◽  
G Protein Coupled

Estrogen receptors (ERs) comprise several nuclear and membrane-bound receptors with different tissue-specific functions. ERα and ERβ are two nuclear members of this family, whereas G protein-coupled estrogen receptor (GPER), ER-X, and Gq-coupled membrane estrogen receptor (Gq-mER) are membrane-bound G protein-coupled proteins. ERα participates in the development and function of several body organs such as the reproductive system, brain, heart and musculoskeletal systems. ERβ has a highly tissue-specific expression pattern, particularly in the female reproductive system, and exerts tumor-suppressive roles in some tissues. Recent studies have revealed functional links between both nuclear and membrane-bound ERs and non-coding RNAs. Several oncogenic lncRNAs and miRNAs have been shown to exert their effects through the modulation of the expression of ERs. Moreover, treatment with estradiol has been shown to alter the malignant behavior of cancer cells through functional axes composed of non-coding RNAs and ERs. The interaction between ERs and non-coding RNAs has functional relevance in several human pathologies associated with estrogen regulation, such as cancers, intervertebral disc degeneration, coronary heart disease and diabetes. In the current review, we summarize scientific literature on the role of miRNAs and lncRNAs on ER-associated signaling and related disorders.

scholarly journals The Potential Role of Seminal Plasma in the Fertilization Outcomes

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Justyna Szczykutowicz ◽  
Anna Kałuża ◽  
Maria Kaźmierowska-Niemczuk ◽  
Mirosława Ferens-Sieczkowska
Keyword(s):  
Seminal Plasma ◽  
Potential Role ◽  
Human Sperm ◽  
Structure And Function ◽  
Regulatory Mechanisms ◽  
Male And Female ◽  
Healthy Pregnancy ◽  
Male Gametes ◽  
And Function

For human infertility both male and female factors may be equally important. Searching for molecular biomarkers of male infertility, neglected for decades, and the attempts to explain regulatory mechanisms of fertilization become thus extremely important. Apart from examination of the structure and function of male gametes, also the possible importance of seminal plasma components should be considered. In this article we discuss data that indicate for the substantial significance of active seminal plasma components for conception and achievement of healthy pregnancy. Seminal plasma impact on the storage and cryopreservation of human and animal sperm and regulatory role of glycodelin on human sperm capacitation as well as hypothesized course of female immune response to allogenic sperm and conceptus has been discussed. The possible involvement of carbohydrates in molecular mechanism of fetoembryonic defense has been also mentioned.

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