Extracellular domains play different roles in gap junction formation and docking compatibility

2014 ◽  
Vol 458 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Donglin Bai ◽  
Ao Hong Wang
Keyword(s):  
Gap Junction ◽  
Molecular Mechanisms ◽  
Bond Forming ◽  
Functional Studies ◽  
Extracellular Domains ◽  
Physiological Processes ◽  
Recent Developments ◽  
Non Covalent Interactions ◽  
Alignment Analysis ◽  
Heterotypic Channels

GJ (gap junction) channels mediate direct intercellular communication and play an important role in many physiological processes. Six connexins oligomerize to form a hemichannel and two hemichannels dock together end-to-end to form a GJ channel. Connexin extracellular domains (E1 and E2) have been shown to be important for the docking, but the molecular mechanisms behind the docking and formation of GJ channels are not clear. Recent developments in atomic GJ structure and functional studies on a series of connexin mutants revealed that E1 and E2 are likely to play different roles in the docking. Non-covalent interactions at the docking interface, including hydrogen bonds, are predicted to form between interdocked extracellular domains. Protein sequence alignment analysis on the docking compatible/incompatible connexins indicate that the E1 domain is important for the formation of the GJ channel and the E2 domain is important in the docking compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming or equivalent residues in both E1 and E2 domains are mutational hot spots for connexin-linked human diseases. Understanding the molecular mechanisms of GJ docking can assist us to develop novel strategies in rescuing the disease-linked connexin mutants.

scholarly journals Pterin-based pigmentation in animals

2021 ◽  
Vol 17 (8) ◽  
pp. 20210221
Author(s):  
Pedro Andrade ◽  
Miguel Carneiro
Keyword(s):  
Molecular Mechanisms ◽  
Potential Model ◽  
Honest Signalling ◽  
Functional Studies ◽  
Physiological Processes ◽  
History Of Research ◽  
Different Types ◽  
Genomic Studies ◽  
History Of ◽  
Advance Research

Pterins are one of the major sources of bright coloration in animals. They are produced endogenously, participate in vital physiological processes and serve a variety of signalling functions. Despite their ubiquity in nature, pterin-based pigmentation has received little attention when compared to other major pigment classes. Here, we summarize major aspects relating to pterin pigmentation in animals, from its long history of research to recent genomic studies on the molecular mechanisms underlying its evolution. We argue that pterins have intermediate characteristics (endogenously produced, typically bright) between two well-studied pigment types, melanins (endogenously produced, typically cryptic) and carotenoids (dietary uptake, typically bright), providing unique opportunities to address general questions about the biology of coloration, from the mechanisms that determine how different types of pigmentation evolve to discussions on honest signalling hypotheses. Crucial gaps persist in our knowledge on the molecular basis underlying the production and deposition of pterins. We thus highlight the need for functional studies on systems amenable for laboratory manipulation, but also on systems that exhibit natural variation in pterin pigmentation. The wealth of potential model species, coupled with recent technological and analytical advances, make this a promising time to advance research on pterin-based pigmentation in animals.

scholarly journals An Evidence-Based Update on the Molecular Mechanisms Underlying Periodontal Diseases

2020 ◽  
Vol 21 (11) ◽  
pp. 3829 ◽  
Author(s):  
Syed Saad B. Qasim ◽  
Dalal Al-Otaibi ◽  
Reham Al-Jasser ◽  
Sarhang S. Gul ◽  
Muhammad Sohail Zafar
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Periodontal Diseases ◽  
Evidence Based ◽  
Oral Diseases ◽  
Cellular Mechanisms ◽  
Ongoing Research ◽  
Physiological Processes ◽  
Recent Developments ◽  
Small Parts

Several investigators have reported about the intricate molecular mechanism underlying periodontal diseases (PD). Nevertheless, the role of specific genes, cells, or cellular mechanisms involved in the pathogenesis of periodontitis are still unclear. Although periodontitis is one of the most prevalent oral diseases globally, there are no pre-diagnostic markers or therapeutic targets available for such inflammatory lesions. A pivotal role is played by pro- and anti-inflammatory markers in modulating pathophysiological and physiological processes in repairing damaged tissues. In addition, effects on osteoimmunology is ever evolving due to the ongoing research in understanding the molecular mechanism lying beneath periodontal diseases. The aim of the current review is to deliver an evidence-based update on the molecular mechanism of periodontitis with a particular focus on recent developments. Reports regarding the molecular mechanism of these diseases have revealed unforeseen results indicative of the fact that significant advances have been made to the periodontal medicine over the past decade. There is integrated hypothesis-driven research going on. Although a wide picture of association of periodontal diseases with immune response has been further clarified with present ongoing research, small parts of the puzzle remain a mystery and require further investigations.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Graphene Oxide and Its Derivatives: Their Synthesis and Use in Organic Synthesis

2019 ◽  
Vol 23 (2) ◽  
pp. 188-204 ◽  
Author(s):  
Xiangjun Peng ◽  
Xianyun Xu ◽  
Fujiang Huang ◽  
Qian Liu ◽  
Liangxian Liu
Keyword(s):  
Graphene Oxide ◽  
Carbon Materials ◽  
Device Fabrication ◽  
Organic Reactions ◽  
Bond Forming ◽  
Bond Forming Reactions ◽  
Modern Physics ◽  
Recent Developments ◽  
Optical And Mechanical Properties ◽  
Nitrogen Double Bond

Since Geim and co-workers reported their groundbreaking experiments on graphene, research on graphene oxide (GO) and its derivatives has greatly influenced the field of modern physics, chemistry, device fabrication, material science, and nanotechnology. The unique structure and fascinating properties of these carbon materials can be ascribed to their eminent chemical, electronic, electrochemical, optical, and mechanical properties of GO and its derivatives, particularly compared to other carbon allotropes. The present Review aims to provide an overview on the recent developments in the preparation of GO and its derivatives and their applications in organic reactions. We will first outline the synthesis of GO and its derivatives. Then, we will discuss the major sections about their application as stoichiometric and catalytic oxidants in organic reactions, a particular emphasis on the carbon-carbon, carbon-oxygen, and carbon-nitrogen single bond-forming reactions, as well as carbon-oxygen and carbon-nitrogen double bond-forming reactions. Simultaneously, this Review also describes briefly transition metal supported on GO or its derivatives as a catalyst for organic reaction. Lastly, we will present an outlook of potential areas where GO and its derivatives may be expected to find utility or opportunity for further growth and study.

scholarly journals The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses

2021 ◽  
Vol 22 (15) ◽  
pp. 8338
Author(s):  
Asad Jan ◽  
Nádia Pereira Gonçalves ◽  
Christian Bjerggaard Vaegter ◽  
Poul Henning Jensen ◽  
Nelson Ferreira
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Alpha Synuclein ◽  
Experimental Models ◽  
Cellular Factors ◽  
Recent Developments ◽  
Novel Targets ◽  
Presynaptic Protein

The pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molecular mechanisms responsible for the spreading of pathological α-syn accumulation in the CNS are not fully understood, growing evidence suggests that de novo α-syn misfolding and/or neuronal internalization of aggregated α-syn facilitates conformational templating of endogenous α-syn monomers in a mechanism reminiscent of prions. A refined understanding of the biochemical and cellular factors mediating the pathological neuron-to-neuron propagation of misfolded α-syn will potentially elucidate the etiology of PD and unravel novel targets for therapeutic intervention. Here, we discuss recent developments on the hypothesis regarding trans-synaptic propagation of α-syn pathology in the context of neuronal vulnerability and highlight the potential utility of novel experimental models of synucleinopathies.

New horizons in mitochondrial contact site research

2020 ◽  
Vol 401 (6-7) ◽  
pp. 793-809
Author(s):  
Naama Zung ◽  
Maya Schuldiner
Keyword(s):  
Endoplasmic Reticulum ◽  
Molecular Mechanisms ◽  
Contact Site ◽  
New Horizons ◽  
Contact Sites ◽  
Future Goals ◽  
Close Proximity ◽  
Recent Developments ◽  
Site Field ◽  
First Contact

AbstractContact sites, areas where two organelles are held in close proximity through the action of molecular tethers, enable non-vesicular communication between compartments. Mitochondria have been center stage in the contact site field since the discovery of the first contact between mitochondria and the endoplasmic reticulum (ER) over 60 years ago. However, only now, in the last decade, has there been a burst of discoveries regarding contact site biology in general and mitochondrial contacts specifically. The number and types of characterized contacts increased dramatically, new molecular mechanisms enabling contact formation were discovered, additional unexpected functions for contacts were shown, and their roles in cellular and organismal physiology were emphasized. Here, we focus on mitochondria as we highlight the most recent developments, future goals and unresolved questions in the field.

scholarly journals Molecular Responses during Plant Grafting and Its Regulation by Auxins, Cytokinins, and Gibberellins

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 397 ◽  
Author(s):  
Anket Sharma ◽  
Bingsong Zheng
Keyword(s):  
Plant Hormones ◽  
Growth And Development ◽  
Molecular Mechanisms ◽  
Main Process ◽  
Graft Union ◽  
Physiological Processes ◽  
Current Review ◽  
Postharvest Life ◽  
Successful Production

Plant grafting is an important horticulture technique used to produce a new plant after joining rootstock and scion. This is one of the most used techniques by horticulturists to enhance the quality and production of various crops. Grafting helps in improving the health of plants, their yield, and the quality of plant products, along with the enhancement of their postharvest life. The main process responsible for successful production of grafted plants is the connection of vascular tissues. This step determines the success rate of grafts and hence needs to be studied in detail. There are many factors that regulate the connection of scion and stock, and plant hormones are of special interest for researchers in the recent times. These phytohormones act as signaling molecules and have the capability of translocation across the graft union. Plant hormones, mainly auxins, cytokinins, and gibberellins, play a major role in the regulation of various key physiological processes occurring at the grafting site. In the current review, we discuss the molecular mechanisms of graft development and the phytohormone-mediated regulation of the growth and development of graft union.

scholarly journals Potassium: A Vital Regulator of Plant Responses and Tolerance to Abiotic Stresses

Agronomy ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 31 ◽  
Author(s):  
Mirza Hasanuzzaman ◽  
M. Bhuyan ◽  
Kamrun Nahar ◽  
Md. Hossain ◽  
Jubayer Mahmud ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Stress Tolerance ◽  
Molecular Mechanisms ◽  
Abiotic Stress Tolerance ◽  
Ion Homeostasis ◽  
Enzyme Activation ◽  
Regulatory Function ◽  
Plant Responses ◽  
Plant Structure ◽  
Physiological Processes

Among the plant nutrients, potassium (K) is one of the vital elements required for plant growth and physiology. Potassium is not only a constituent of the plant structure but it also has a regulatory function in several biochemical processes related to protein synthesis, carbohydrate metabolism, and enzyme activation. Several physiological processes depend on K, such as stomatal regulation and photosynthesis. In recent decades, K was found to provide abiotic stress tolerance. Under salt stress, K helps to maintain ion homeostasis and to regulate the osmotic balance. Under drought stress conditions, K regulates stomatal opening and helps plants adapt to water deficits. Many reports support the notion that K enhances antioxidant defense in plants and therefore protects them from oxidative stress under various environmental adversities. In addition, this element provides some cellular signaling alone or in association with other signaling molecules and phytohormones. Although considerable progress has been made in understanding K-induced abiotic stress tolerance in plants, the exact molecular mechanisms of these protections are still under investigation. In this review, we summarized the recent literature on the biological functions of K, its uptake, its translocation, and its role in plant abiotic stress tolerance.

Stable transfer and restricted expression of a cloned class I gene encoding a secreted transplantation-like antigen

1985 ◽  
Vol 5 (6) ◽  
pp. 1295-1300
Author(s):  
Y Barra ◽  
K Tanaka ◽  
K J Isselbacher ◽  
G Khoury ◽  
G Jay
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Class I ◽  
Regulatory Sequences ◽  
Transcriptional Enhancer ◽  
Gene Encoding ◽  
Specific Expression ◽  
Tissue Specific ◽  
Functional Studies ◽  
I Gene

The identification of a unique major histocompatibility complex class I gene, designated Q10, which encodes a secreted rather than a cell surface antigen has led to questions regarding its potential role in regulating immunological functions. Since the Q10 gene is specifically activated only in the liver, we sought to define the molecular mechanisms which control its expression in a tissue-specific fashion. Results obtained by transfection of the cloned Q10 gene, either in the absence or presence of a heterologous transcriptional enhancer, into a variety of cell types of different tissue derivations are consistent with the Q10 gene being regulated at two levels. The first is by a cis-dependent mechanism which appears to involve site-specific DNA methylation. The second is by a trans-acting mechanism which would include the possibility of an enhancer binding factor. The ability to efficiently express the Q10 gene in certain transfected cell lines offers an opportunity to obtain this secreted class I antigen in quantities sufficient for functional studies; this should also make it possible to define regulatory sequences which may be responsible for the tissue-specific expression of Q10.

Multiple mechanisms are responsible for altered expression of gap junction genes during oncogenesis in rat liver

1994 ◽  
Vol 107 (1) ◽  
pp. 83-95
Author(s):  
M.J. Neveu ◽  
J.R. Hully ◽  
K.L. Babcock ◽  
E.L. Hertzberg ◽  
B.J. Nicholson ◽  
...  
Keyword(s):  
Gap Junction ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Northern Blotting ◽  
Mrna Abundance ◽  
Common Mechanism ◽  
Cx43 Expression ◽  
Bile Duct Proliferation ◽  
Altered Expression ◽  
Connexin Expression

Although several abnormalities in gap junction (GJ) structure and/or function have been described in neoplasms, the molecular mechanisms responsible for many of the alterations remain unknown. The identification of a family of GJ proteins, termed connexins, prompted this study of connexin32 (Cx32), connexin26 (Cx26) and connexin43 (Cx43) expression during rat hepatocarcinogenesis. Using antibody, cDNA and cRNA probes, we investigated connexin mRNA and protein expression in preneoplastic and neoplastic rat livers. In normal liver, Cx32 is expressed in hepatocytes throughout the hepatic acinus, Cx26 is restricted to periportal hepatocytes, and Cx43 is expressed by mesothelial cells forming Glisson's capsule. Most preneoplastic altered hepatic foci generated by diethylnitrosamine (DEN) initiation and either phenobarbital (PB) or 2,3,7,8-dichlorodibenzo-p-dioxin (TCDD) promotion exhibited decreased Cx32 or increased Cx26 staining. Foci from either protocol failed to display Cx43 immunoreactivity. In the majority of PB-promoted foci, Cx32 immunoreactivity decreased independently of changes in mRNA abundance. Continuous thymidine labeling, following cessation of PB promotion, showed that downregulation of Cx32 staining is reversible in foci that are promoter-dependent for growth, but irreversible in lesions that are promoter-independent for growth. Hepatic neoplasms from rats initiated with DEN and promoted with PB or TCDD also displayed modified connexin expression. While all 24 neoplasms studied were deficient in normal punctate Cx32 and Cx26 staining, altered cellular localization of these proteins was apparent in some tumors. Immunoblotting of crude tissue extracts revealed that neoplasms with disordered Cx32 staining showed immunoreactive bands with altered electrophoretic mobility. These observations show that hepatomas may downregulate Cx32 expression through changes in the primary structure of Cx32 or by post-translational modifications. Northern blotting of total tumor mRNAs failed to demonstrate consistent changes in the abundance of Cx32, Cx26 or Cx43 transcripts. Some tumors expressed steady-state transcripts without observable immunoreactivity, indicating that some hepatomas downregulate connexin immunoreactivity independently of mRNA abundance. Increased levels of Cx43 mRNA and protein were found in several neoplasms, but immunostaining was always localized to nonparenchymal cells. Areas of bile duct proliferation and cholangiomas displayed Cx43 staining, whereas, cholangiocarcinomas were deficient in immunoreactivity. These findings show that alterations in the expression of connexins, by either downregulation or differential induction, represent common modifications during hepatocarcinogenesis. Although our results imply that connexins represent useful markers for the boundary between tumor promotion and progression, preneoplastic and neoplastic rat hepatocytes fail to use a common mechanism to modify connexin expression.

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