scholarly journals Functional Mechanism of Proton Pump-Type Rhodopsins Found in Various Microorganisms as a Potential Effective Tool in Optogenetics

2021 ◽  
Author(s):  
Jun Tamogami ◽  
Takashi Kikukawa
Keyword(s):  
Neural Activity ◽  
Molecular Mechanisms ◽  
Proton Pumps ◽  
Ion Pumps ◽  
Future Prospects ◽  
Microbial World ◽  
Distinctive Features ◽  
Functional Mechanism ◽  
Retinal Chromophore ◽  
Intensive Investigation

Microbial rhodopsins, which are photoreceptive membrane proteins consisting of seven α-helical structural apoproteins (opsin) and a covalently attached retinal chromophore, are one of the most frequently used optogenetic tools. Since the first success of neuronal activation by channelrhodopsin, various microbial rhodopsins functioning as ion channels or pumps have been applied to optogenetics. The use of light-driven ion pumps to generate large negative membrane potentials allows the silencing of neural activity. Although anion-conductive channelrhodopsins have been recently discovered, light-driven outward H+-pumping rhodopsins, which can generate a larger photoinduced current than a light-driven inward Cl−-pump halorhodopsin, must be more efficient tools for this purpose and have been often utilized for optogenetics. There are abundant proton pumps in the microbial world, providing numerous candidates for potential practical optogenetic instruments. In addition, their distinctive features (that is, being accompanied by photoinduced intracellular pH changes) could enable expansion of this technique to versatile applications. Thus, intensive investigation of the molecular mechanisms of various microbial H+-pumps may be useful for the exploration of more potent tools and the creation of effectively designed mutants. In this chapter, we focus on the functional mechanism of microbial H+-pumping rhodopsins. Further, we describe the future prospects of these rhodopsins for optogenetic applications.

scholarly journals Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

2008 ◽  
Vol 36 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Yong Liu ◽  
Ravinder J. Singh ◽  
Kristie Usa ◽  
Brian C. Netzel ◽  
Mingyu Liang
Keyword(s):  
Blood Pressure ◽  
Urinary Excretion ◽  
Molecular Mechanisms ◽  
Renal Medulla ◽  
Hydroxysteroid Dehydrogenase ◽  
Induced Hypertension ◽  
Intensive Investigation ◽  
Salt Sensitive Hypertension ◽  
Interfering Rna

The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11β-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11β-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11β-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocorticosterone to active corticosterone. The urinary corticosterone/11-dehydrocorticosterone ratio as well as urinary excretion of corticosterone was higher in Dahl salt-sensitive rats than in SS-13BN rats. Knockdown of renal medullary 11β-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinary excretion of corticosterone. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13BN rats. Long-term attenuation of salt-induced hypertension was achieved with small hairpin RNA targeting renal medullary 11β-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11β-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.

scholarly journals The Making of Long-Lasting Memories: A Fruit Fly Perspective

2021 ◽  
Vol 15 ◽  
Author(s):  
Camilla Roselli ◽  
Mani Ramaswami ◽  
Tamara Boto ◽  
Isaac Cervantes-Sandoval
Keyword(s):  
Learning And Memory ◽  
Neural Activity ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Fruit Fly ◽  
Memory Formation ◽  
Synaptic Activity ◽  
Model Organisms ◽  
Transient Wave ◽  
Control Of Gene Expression

Understanding the nature of the molecular mechanisms underlying memory formation, consolidation, and forgetting are some of the fascinating questions in modern neuroscience. The encoding, stabilization and elimination of memories, rely on the structural reorganization of synapses. These changes will enable the facilitation or depression of neural activity in response to the acquisition of new information. In other words, these changes affect the weight of specific nodes within a neural network. We know that these plastic reorganizations require de novo protein synthesis in the context of Long-term memory (LTM). This process depends on neural activity triggered by the learned experience. The use of model organisms like Drosophila melanogaster has been proven essential for advancing our knowledge in the field of neuroscience. Flies offer an optimal combination of a more straightforward nervous system, composed of a limited number of cells, and while still displaying complex behaviors. Studies in Drosophila neuroscience, which expanded over several decades, have been critical for understanding the cellular and molecular mechanisms leading to the synaptic and behavioral plasticity occurring in the context of learning and memory. This is possible thanks to sophisticated technical approaches that enable precise control of gene expression in the fruit fly as well as neural manipulation, like chemogenetics, thermogenetics, or optogenetics. The search for the identity of genes expressed as a result of memory acquisition has been an active interest since the origins of behavioral genetics. From screenings of more or less specific candidates to broader studies based on transcriptome analysis, our understanding of the genetic control behind LTM has expanded exponentially in the past years. Here we review recent literature regarding how the formation of memories induces a rapid, extensive and, in many cases, transient wave of transcriptional activity. After a consolidation period, transcriptome changes seem more stable and likely represent the synthesis of new proteins. The complexity of the circuitry involved in memory formation and consolidation is such that there are localized changes in neural activity, both regarding temporal dynamics and the nature of neurons and subcellular locations affected, hence inducing specific temporal and localized changes in protein expression. Different types of neurons are recruited at different times into memory traces. In LTM, the synthesis of new proteins is required in specific subsets of cells. This de novo translation can take place in the somatic cytoplasm and/or locally in distinct zones of compartmentalized synaptic activity, depending on the nature of the proteins and the plasticity-inducing processes that occur. We will also review recent advances in understanding how localized changes are confined to the relevant synapse. These recent studies have led to exciting discoveries regarding proteins that were not previously involved in learning and memory processes. This invaluable information will lead to future functional studies on the roles that hundreds of new molecular actors play in modulating neural activity.

scholarly journals The Anticancer Effects of Paeoniflorin and Its Underlying Mechanisms

2019 ◽  
Vol 14 (9) ◽  
pp. 1934578X1987640
Author(s):  
Li-Juan Deng ◽  
Yu-He Lei ◽  
Tsz-Fung Chiu ◽  
Ming Qi ◽  
Hua Gan ◽  
...  
Keyword(s):  
Recent Progress ◽  
Antitumor Effect ◽  
Molecular Mechanisms ◽  
Experimental Studies ◽  
Future Prospects ◽  
Anticancer Effects ◽  
Wide Range ◽  
Underlying Mechanisms

Paeoniflorin (PF) is an important pharmacological component of some Chinese traditional herbal formulas, such as Bai Shao, Chi Shao, and Dan Pi, which have been clinically used for centuries. Although many experimental studies have explored a wide range of pharmacological properties of PF, including anticancer, anti-inflammatory, antioxidant, immunoregulatory, and prevention of insulin resistance, there is no review to describe these reported effects systematically, especially the antitumor effect and the underlying mechanisms. In this review, we summarize the recent progress on the anticancer profiles both in vitro and in vivo of PF. Moreover, we highlight the integrated molecular mechanisms of PF and contemplate its future prospects as a potential anticancer drug.

Melanosomes on the move: a model to understand organelle dynamics

2011 ◽  
Vol 39 (5) ◽  
pp. 1191-1196 ◽  
Author(s):  
Alistair N. Hume ◽  
Miguel C. Seabra
Keyword(s):  
Intracellular Transport ◽  
Motor Proteins ◽  
Molecular Mechanisms ◽  
Pigment Cells ◽  
Future Prospects ◽  
Dynamic Nature ◽  
Live Cell Microscopy ◽  
Intracellular Organelles ◽  
Cell Microscopy ◽  
Shed Light

Advances in live-cell microscopy have revealed the extraordinarily dynamic nature of intracellular organelles. Moreover, movement appears to be critical in establishing and maintaining intracellular organization and organellar and cellular function. Motility is regulated by the activity of organelle-associated motor proteins, kinesins, dyneins and myosins, which move cargo along polar MT (microtubule) and actin tracks. However, in most instances, the motors that move specific organelles remain mysterious. Over recent years, pigment granules, or melanosomes, within pigment cells have provided an excellent model for understanding the molecular mechanisms by which motor proteins associate with and move intracellular organelles. In the present paper, we discuss recent discoveries that shed light on the mechanisms of melanosome transport and highlight future prospects for the use of pigment cells in unravelling general molecular mechanisms of intracellular transport.

scholarly journals Dendritic Spines and Development: Towards a Unifying Model of Spinogenesis—A Present Day Review of Cajal's Histological Slides and Drawings

2010 ◽  
Vol 2010 ◽  
pp. 1-29 ◽  
Author(s):  
Pablo García-López ◽  
Virginia García-Marín ◽  
Miguel Freire
Keyword(s):  
Central Nervous System ◽  
Dendritic Spines ◽  
Neural Activity ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Practical Interest ◽  
High Quality ◽  
Spine Development ◽  
Dimensional Reconstruction ◽  
The Central Nervous System

Dendritic spines receive the majority of excitatory connections in the central nervous system, and, thus, they are key structures in the regulation of neural activity. Hence, the cellular and molecular mechanisms underlying their generation and plasticity, both during development and in adulthood, are a matter of fundamental and practical interest. Indeed, a better understanding of these mechanisms should provide clues to the development of novel clinical therapies. Here, we present original results obtained from high-quality images of Cajal's histological preparations, stored at the Cajal Museum (Instituto Cajal, CSIC), obtained using extended focus imaging, three-dimensional reconstruction, and rendering. Based on the data available in the literature regarding the formation of dendritic spines during development and our results, we propose a unifying model for dendritic spine development.

scholarly journals X-Chromosome Inactivation and Autosomal Random Monoallelic Expression as “Faux Amis”

2021 ◽  
Vol 9 ◽  
Author(s):  
Vasco M. Barreto ◽  
Nadiya Kubasova ◽  
Clara F. Alves-Pereira ◽  
Anne-Valerie Gendrel
Keyword(s):  
X Chromosome ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Phenotypic Diversity ◽  
X Chromosome Inactivation ◽  
Cellular Level ◽  
Chromosome Inactivation ◽  
Monoallelic Expression ◽  
Distinctive Features ◽  
Faux Amis

X-chromosome inactivation (XCI) and random monoallelic expression of autosomal genes (RMAE) are two paradigms of gene expression regulation where, at the single cell level, genes can be expressed from either the maternal or paternal alleles. X-chromosome inactivation takes place in female marsupial and placental mammals, while RMAE has been described in mammals and also other species. Although the outcome of both processes results in random monoallelic expression and mosaicism at the cellular level, there are many important differences. We provide here a brief sketch of the history behind the discovery of XCI and RMAE. Moreover, we review some of the distinctive features of these two phenomena, with respect to when in development they are established, their roles in dosage compensation and cellular phenotypic diversity, and the molecular mechanisms underlying their initiation and stability.

scholarly journals Seasonal regulation of singing-driven gene expression associated with song plasticity in the canary, an open-ended vocal learner

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shin Hayase ◽  
Chengru Shao ◽  
Masahiko Kobayashi ◽  
Chihiro Mori ◽  
Wan-chun Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Activity ◽  
Molecular Mechanisms ◽  
Vocal Learning ◽  
Motor Nucleus ◽  
Vocal Plasticity ◽  
Learning Capacity ◽  
Induction Rate ◽  
Song Acquisition ◽  
Activity Dependent

AbstractSongbirds are one of the few animal taxa that possess vocal learning abilities. Different species of songbirds exhibit species-specific learning programs during song acquisition. Songbirds with open-ended vocal learning capacity, such as the canary, modify their songs during adulthood. Nevertheless, the neural molecular mechanisms underlying open-ended vocal learning are not fully understood. We investigated the singing-driven expression of neural activity-dependent genes (Arc, Egr1, c-fos, Nr4a1, Sik1, Dusp6, and Gadd45β) in the canary to examine a potential relationship between the gene expression level and the degree of seasonal vocal plasticity at different ages. The expression of these genes was differently regulated throughout the critical period of vocal learning in the zebra finch, a closed-ended song learner. In the canary, the neural activity-dependent genes were induced by singing in the song nuclei throughout the year. However, in the vocal motor nucleus, the robust nucleus of the arcopallium (RA), all genes were regulated with a higher induction rate by singing in the fall than in the spring. The singing-driven expression of these genes showed a similar induction rate in the fall between the first year juvenile and the second year adult canaries, suggesting a seasonal, not age-dependent, regulation of the neural activity-dependent genes. By measuring seasonal vocal plasticity and singing-driven gene expression, we found that in RA, the induction intensity of the neural activity-dependent genes was correlated with the state of vocal plasticity. These results demonstrate a correlation between vocal plasticity and the singing-driven expression of neural activity-dependent genes in RA through song development, regardless of whether a songbird species possesses an open- or closed-ended vocal learning capacity.

scholarly journals Lokiarchaeota archaeon schizorhodopsin-2 (LaSzR2) is an inward proton pump displaying a characteristic feature of acid-induced spectral blue-shift

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Keiichi Kojima ◽  
Susumu Yoshizawa ◽  
Masumi Hasegawa ◽  
Masaki Nakama ◽  
Marie Kurihara ◽  
...  
Keyword(s):  
Schiff Base ◽  
Proton Pump ◽  
Flash Photolysis ◽  
Blue Shift ◽  
Spectroscopic Studies ◽  
Spectral Shift ◽  
Bulk Solution ◽  
Proton Pumps ◽  
Ph Titration ◽  
Retinal Chromophore

AbstractThe photoreactive protein rhodopsin is widespread in microorganisms and has a variety of photobiological functions. Recently, a novel phylogenetically distinctive group named ‘schizorhodopsin (SzR)’ has been identified as an inward proton pump. We performed functional and spectroscopic studies on an uncharacterised schizorhodopsin from the phylum Lokiarchaeota archaeon. The protein, LaSzR2, having an all-trans-retinal chromophore, showed inward proton pump activity with an absorption maximum at 549 nm. The pH titration experiments revealed that the protonated Schiff base of the retinal chromophore (Lys188, pKa = 12.3) is stabilised by the deprotonated counterion (presumably Asp184, pKa = 3.7). The flash-photolysis experiments revealed the presence of two photointermediates, K and M. A proton was released and uptaken from bulk solution upon the formation and decay of the M intermediate. During the M-decay, the Schiff base was reprotonated by the proton from a proton donating residue (presumably Asp172). These properties were compared with other inward (SzRs and xenorhodopsins, XeRs) and outward proton pumps. Notably, LaSzR2 showed acid-induced spectral ‘blue-shift’ due to the protonation of the counterion, whereas outward proton pumps showed opposite shifts (red-shifts). Thus, we can distinguish between inward and outward proton pumps by the direction of the acid-induced spectral shift.

scholarly journals Omeprazole Promotes Chloride Exclusion and Induces Salt Tolerance in Greenhouse Basil

Agronomy ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 355 ◽  
Author(s):  
Petronia Carillo ◽  
Pasqualina Woodrow ◽  
Giampaolo Raimondi ◽  
Christophe El-Nakhel ◽  
Antonio Pannico ◽  
...  
Keyword(s):  
Salt Tolerance ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Benzimidazole Derivative ◽  
Ion Homeostasis ◽  
Chloride Concentration ◽  
Co2 Assimilation ◽  
Stomatal Resistance ◽  
Bioactive Molecules ◽  
Proton Pumps

The role of small bioactive molecules (<500 Da) in mechanisms improving resource use efficiency in plants under stress conditions draws increasing interest. One such molecule is omeprazole (OMP), a benzimidazole derivative and inhibitor of animal proton pumps shown to improve nitrate uptake and exclusion of toxic ions, especially of chloride from the cytosol of salt-stressed leaves. Currently, OMP was applied as substrate drench at two rates (0 or 10 μM) on hydroponic basil (Ocimum basilicum L. cv. Genovese) grown under decreasing NO3−:Cl− ratio (80:20, 60:40, 40:60, or 20:80). Chloride concentration and stomatal resistance increased while transpiration, net CO2 assimilation rate and beneficial ions (NO3−, PO43−, and SO42−) decreased with reduced NO3−:Cl− ratio under the 0 μM OMP treatment. The negative effects of chloride were not only mitigated by the 10 μM OMP application in all treatments, with the exception of 20:80 NO3−:Cl−, but plant growth at 80:20, 60:40, and 40:60 NO3−:Cl− ratios receiving OMP application showed maximum fresh yield (+13%, 24%, and 22%, respectively), shoot (+10%, 25%, and 21%, respectively) and root (+32%, 76%, and 75%, respectively) biomass compared to the corresponding untreated treatments. OMP was not directly involved in ion homeostasis and compartmentalization of vacuolar or apoplastic chloride. However, it was active in limiting chloride loading into the shoot, as manifested by the lower chloride concentration in the 80:20, 60:40, and 40:60 NO3−:Cl− treatments compared to the respective controls (−41%, −37%, and −24%), favoring instead that of nitrate and potassium while also boosting photosynthetic activity. Despite its unequivocally beneficial effect on plants, the large-scale application of OMP is currently limited by the molecule’s high cost. However, further studies are warranted to unravel the molecular mechanisms of OMP-induced reduction of chloride loading to shoot and improved salt tolerance.

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