scholarly journals Emerging concepts regarding pannexin 1 in the vasculature

2015 ◽  
Vol 43 (3) ◽  
pp. 495-501 ◽  
Author(s):  
Miranda E. Good ◽  
Daniela Begandt ◽  
Leon J. DeLalio ◽  
Alexander S. Keller ◽  
Marie Billaud ◽  
...  
Keyword(s):  
Vascular Function ◽  
Atp Release ◽  
The Body ◽  
Purinergic Signalling ◽  
Molecular Tools ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Pannexin 1 ◽  
Knockout Animals

Pannexin channels are newly discovered ATP release channels expressed throughout the body. Pannexin 1 (Panx1) channels have become of great interest as they appear to participate in a multitude of signalling cascades, including regulation of vascular function. Although numerous Panx1 pharmacological inhibitors have been discovered, these inhibitors are not specific for Panx1 and have additional effects on other proteins. Therefore, molecular tools, such as RNA interference and knockout animals, are needed to demonstrate the role of pannexins in various cellular functions. This review focuses on the known roles of Panx1 related to purinergic signalling in the vasculature focusing on post-translational modifications and channel gating mechanisms that may participate in the regulated release of ATP.

scholarly journals Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 272 ◽  
Author(s):  
Ksenia Timonina ◽  
Anna Kotova ◽  
Georg Zoidl
Keyword(s):  
Atp Release ◽  
Integral Membrane Protein ◽  
Membrane Channel ◽  
Release Channel ◽  
Post Translational Modifications ◽  
Mutant Proteins ◽  
Pannexin 1 ◽  
Interaction Testing ◽  
Insight Into

Pannexin 1 (Panx1) is a ubiquitously expressed hexameric integral membrane protein known to function as an adenosine triphosphate (ATP) release channel. Panx1 proteins exist in unglycosylated core form (Gly0). They undergo critical post-translational modifications forming the high mannose glycosylation state (Gly1) in the endoplasmic reticulum (ER) and the complex glycosylation state (Gly2) in the Golgi apparatus. The regulation of transition from the ER to the cell membrane is not fully understood. Using site-specific mutagenesis, dye uptake assays, and interaction testing, we identified two conserved aromatic residues, Trp123 and Tyr205, in the transmembrane domains 2 and 3 of the zebrafish panx1a protein. Results suggest that both residues primarily govern the assembly of panx1a subunits into channels, with mutant proteins failing to interact. The results provide insight into a mechanism enabling regulation of Panx1 oligomerization, glycosylation, and trafficking.

scholarly journals The role of pannexin 1 hemichannels in ATP release and cell-cell communication in mouse taste buds

2007 ◽  
Vol 104 (15) ◽  
pp. 6436-6441 ◽  
Author(s):  
Y.-J. Huang ◽  
Y. Maruyama ◽  
G. Dvoryanchikov ◽  
E. Pereira ◽  
N. Chaudhari ◽  
...  
Keyword(s):  
Cell Communication ◽  
Atp Release ◽  
Taste Buds ◽  
Pannexin 1 ◽  
Mouse Taste ◽  
Cell Cell

scholarly journals Cardiomyocyte differentiation from iPS cells is delayed following knockout of Bcl-2

2022 ◽  
Author(s):  
Tim Vervliet ◽  
Robin Duelen ◽  
lLewelyn H Roderick ◽  
Maurilio Sampaolesi
Keyword(s):  
Cell Death ◽  
Pluripotent Stem Cells ◽  
Direct Interaction ◽  
B Cell Lymphoma ◽  
Ips Cells ◽  
Cardiomyocyte Differentiation ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Induced Pluripotent

Anti-apoptotic B-cell lymphoma 2 (Bcl-2) regulates a wide array of cellular functions involved in cell death, cell survival decisions and autophagy. Bcl-2 acts by both direct interaction with different components of the pathways involved and by intervening in intracellular Ca2+ signalling. The function of Bcl-2 is in turn regulated by post-translational modifications including phosphorylation at different sites by various kinases. Besides functions in cell death and apoptosis, Bcl-2 regulates cell differentiation processes, including of cardiomyocytes, although the signalling pathways involved are not fully elucidated. To further address the role of Bcl-2 during cardiomyocyte differentiation, we investigated the effect of its genetic knockout by CRISPR/Cas9 on the differentiation and functioning of human induced pluripotent stem cells to cardiomyocytes. Our results indicate that differentiation of iPS cells to cardiomyocytes is delayed by Bcl-2 KO, resulting in reduced size of spontaneously beating cells and reduced expression of cardiomyocyte Ca2+ toolkit and functionality. These data thus indicate that Bcl-2 an essential protein for cardiomyocyte generation.

scholarly journals Post-Translational S-Nitrosylation of Proteins in Regulating Cardiac Oxidative Stress

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1051 ◽  
Author(s):  
Xiaomeng Shi ◽  
Hongyu Qiu
Keyword(s):  
Therapeutic Potential ◽  
Heart Diseases ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Cardiac Protection ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Redox ◽  
Novel Therapeutic Strategies

Like other post-translational modifications (PTMs) of proteins, S-nitrosylation has been considered a key regulatory mechanism of multiple cellular functions in many physiological and disease conditions. Emerging evidence has demonstrated that S-nitrosylation plays a crucial role in regulating redox homeostasis in the stressed heart, leading to discoveries in the mechanisms underlying the pathogenesis of heart diseases and cardiac protection. In this review, we summarize recent studies in understanding the molecular and biological basis of S-nitrosylation, including the formation, spatiotemporal specificity, homeostatic regulation, and association with cellular redox status. We also outline the currently available methods that have been applied to detect S-nitrosylation. Additionally, we synopsize the up-to-date studies of S-nitrosylation in various cardiac diseases in humans and animal models, and we discuss its therapeutic potential in cardiac protection. These pieces of information would bring new insights into understanding the role of S-nitrosylation in cardiac pathogenesis and provide novel avenues for developing novel therapeutic strategies for heart diseases.

A pannexin 1 channelopathy causes human oocyte death

2019 ◽  
Vol 11 (485) ◽  
pp. eaav8731 ◽  
Author(s):  
Qing Sang ◽  
Zhihua Zhang ◽  
Juanzi Shi ◽  
Xiaoxi Sun ◽  
Bin Li ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Critical Role ◽  
Atp Release ◽  
Cellular Communication ◽  
Human Oocyte ◽  
Channel Activity ◽  
Glycosylation Pattern ◽  
Pannexin 1 ◽  
Independent Families

Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms three species, GLY0, GLY1, and GLY2. Here, we describe four independent families in which mutations in PANX1 cause familial or sporadic female infertility via a phenotype that we term “oocyte death.” The mutations, which are associated with oocyte death, alter the PANX1 glycosylation pattern, influence the subcellular localization of PANX1 in cultured cells, and result in aberrant PANX1 channel activity, ATP release in oocytes, and mutant PANX1 GLY1. Overexpression of a patient-derived mutation in mice causes infertility, recapitulating the human oocyte death phenotype. Our findings demonstrate the critical role of PANX1 in human oocyte development, provide a genetic explanation for a subtype of infertility, and suggest a potential target for therapeutic intervention for this disease.

scholarly journals The Role of Post-Translational Modifications in the Phase Transitions of Intrinsically Disordered Proteins

2019 ◽  
Vol 20 (21) ◽  
pp. 5501 ◽  
Author(s):  
Izzy Owen ◽  
Frank Shewmaker
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Genomics And Proteomics ◽  
Eukaryotic Proteomes

Advances in genomics and proteomics have revealed eukaryotic proteomes to be highly abundant in intrinsically disordered proteins that are susceptible to diverse post-translational modifications. Intrinsically disordered regions are critical to the liquid–liquid phase separation that facilitates specialized cellular functions. Here, we discuss how post-translational modifications of intrinsically disordered protein segments can regulate the molecular condensation of macromolecules into functional phase-separated complexes.

scholarly journals Identification of Pannexins in Rat Nasal Mucosa

2013 ◽  
Vol 4 (2) ◽  
pp. ar.2013.4.0052 ◽  
Author(s):  
Toyoaki Ohbuchi ◽  
Nobusuke Hohchi ◽  
Jun-ichi Ohkubo ◽  
Koichi Hashida ◽  
Hiroki Koizumi ◽  
...  
Keyword(s):  
Atp Release ◽  
Upper Airway ◽  
Rt Pcr ◽  
Cellular Functions ◽  
Adult Rats ◽  
Airway Epithelia ◽  
Pannexin 1 ◽  
Male Wistar Rats ◽  
Atp Signaling ◽  
Fluorescence Immunohistochemistry

Pannexins are a second family of gap-junction proteins in vertebrates, classified as pannexin-1, pannexin-2, and pannexin-3. Pannexin-1 is one of the candidates for channel-mediated ATP release into the extracellular space. In airway epithelia, ATP signaling modulates multiple cellular functions such as mucus/ion secretion and mucociliary clearance systems. However, the expression of pannexins in the upper airway has not been investigated. Nasal septal mucosae were collected from adult male Wistar rats aged 20–24 weeks. The expression of pannexin-1, pannexin-2, and pannexin-3 was examined by reverse transcription polymerase chain reaction (RT-PCR) and by whole-mount fluorescence immunohistochemistry. Transcripts for pannexin-1, pannexin-2, and pannexin-3 were detected in nasal septal mucosae of adult rats by RT-PCR. Distinct immunohistochemical fluorescence for pannexin-1 was observed in the epithelial layer, whereas there was no immunoreactivity for pannexin-2 or pannexin-3. This is the first article establishing the existence of pannexins (predominantly pannexin-1) in the upper airway, suggesting their possible participation in the physiological functions of ATP release and signaling in this tissue.

scholarly journals Role of Metabolism in Bone Development and Homeostasis

2020 ◽  
Vol 21 (23) ◽  
pp. 8992
Author(s):  
Akiko Suzuki ◽  
Mina Minamide ◽  
Chihiro Iwaya ◽  
Kenichi Ogata ◽  
Junichi Iwata
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Diseases ◽  
Bone Cells ◽  
Bone Development ◽  
Bone Matrix ◽  
The Body ◽  
Cellular Functions ◽  
Genetic Studies ◽  
Cellular Dysfunction

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.

FoxO transcription factors in oxidative stress response and ageing – a new fork on the way to longevity?

2008 ◽  
Vol 389 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Daniel G. Sedding
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Effects ◽  
Forkhead Box ◽  
Foxo Transcription Factors

Abstract Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxidative stress and ageing. FoxOs are regulated by a variety of different growth factors and hormones, and their activity is tightly controlled by post-translational modifications, including phosphorylation, acetylation, ubiquitination and interaction with different proteins and transcription factors. This brief review focuses on the molecular mechanisms, cellular effects and resulting organismal phenotypes generated by differentially regulated FoxO proteins and discusses our current understanding of the role of FoxOs in disease and ageing processes.

scholarly journals New developments in probing and targeting protein acylation in malaria, leishmaniasis and African sleeping sickness

Parasitology ◽  
2017 ◽  
Vol 145 (2) ◽  
pp. 157-174 ◽  
Author(s):  
MARKUS RITZEFELD ◽  
MEGAN H. WRIGHT ◽  
EDWARD W. TATE
Keyword(s):  
Drug Targets ◽  
Leishmania Donovani ◽  
Protozoan Parasites ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
New Developments ◽  
Tropical Regions ◽  
Novel Drug ◽  
Protein Lipidation

SUMMARYInfections by protozoan parasites, such as Plasmodium falciparum or Leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. The increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. Post-translational modifications (PTMs) are important modulators of biology and inhibition of protein lipidation has emerged as a promising therapeutic strategy for treatment of parasitic diseases. In this review we summarize the latest insights into protein lipidation in protozoan parasites. We discuss how recent chemical proteomic approaches have delivered the first global overviews of protein lipidation in these organisms, contributing to our understanding of the role of this PTM in critical metabolic and cellular functions. Additionally, we highlight the development of new small molecule inhibitors to target parasite acyl transferases.

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