scholarly journals TMEM266 is a functional voltage sensor regulated by extracellular Zn2+

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ferenc Papp ◽  
Suvendu Lomash ◽  
Orsolya Szilagyi ◽  
Erika Babikow ◽  
Jaime Smith ◽  
...  
Keyword(s):  
Ion Channels ◽  
Unknown Function ◽  
Conformational Transition ◽  
Voltage Sensor ◽  
Structural Rearrangements ◽  
Future Studies ◽  
Proton Channels ◽  
Cellular Processes ◽  
Electrical Signaling ◽  
And Control

Voltage-activated ion channels contain S1-S4 domains that sense membrane voltage and control opening of ion-selective pores, a mechanism that is crucial for electrical signaling. Related S1-S4 domains have been identified in voltage-sensitive phosphatases and voltage-activated proton channels, both of which lack associated pore domains. hTMEM266 is a protein of unknown function that is predicted to contain an S1-S4 domain, along with partially structured cytoplasmic termini. Here we show that hTMEM266 forms oligomers, undergoes both rapid (µs) and slow (ms) structural rearrangements in response to changes in voltage, and contains a Zn2+ binding site that can regulate the slow conformational transition. Our results demonstrate that the S1-S4 domain in hTMEM266 is a functional voltage sensor, motivating future studies to identify cellular processes that may be regulated by the protein. The ability of hTMEM266 to respond to voltage on the µs timescale may be advantageous for designing new genetically encoded voltage indicators.

scholarly journals Roles of Microglial Ion Channel in Neurodegenerative Diseases

2021 ◽  
Vol 10 (6) ◽  
pp. 1239
Author(s):  
Alexandru Cojocaru ◽  
Emilia Burada ◽  
Adrian-Tudor Bălșeanu ◽  
Alexandru-Florian Deftu ◽  
Bogdan Cătălin ◽  
...  
Keyword(s):  
Ion Channels ◽  
Neurodegenerative Diseases ◽  
Excitable Cells ◽  
Proton Channels ◽  
Voltage Gated ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
The Common ◽  
Transient Receptor ◽  
The Impact

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.

scholarly journals Hypoxia. 4. Hypoxia and ion channel function

2011 ◽  
Vol 300 (5) ◽  
pp. C951-C967 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Jan Polak
Keyword(s):  
Ion Channels ◽  
Cell Function ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Cell Types ◽  
Cellular Processes ◽  
Oxygen Sensitive ◽  
Sense And Respond ◽  
And Function ◽  
And Control

The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes.

scholarly journals Tarantula Toxins Interact with Voltage Sensors within Lipid Membranes

2007 ◽  
Vol 130 (5) ◽  
pp. 497-511 ◽  
Author(s):  
Mirela Milescu ◽  
Jan Vobecky ◽  
Soung H. Roh ◽  
Sung H. Kim ◽  
Hoi J. Jung ◽  
...  
Keyword(s):  
Ion Channels ◽  
Lipid Membranes ◽  
Voltage Sensor ◽  
Structural Motif ◽  
Membrane Interaction ◽  
Voltage Sensors ◽  
Kv Channels ◽  
Channel Interactions ◽  
The Stability ◽  
Electrical Signaling

Voltage-activated ion channels are essential for electrical signaling, yet the mechanism of voltage sensing remains under intense investigation. The voltage-sensor paddle is a crucial structural motif in voltage-activated potassium (Kv) channels that has been proposed to move at the protein–lipid interface in response to changes in membrane voltage. Here we explore whether tarantula toxins like hanatoxin and SGTx1 inhibit Kv channels by interacting with paddle motifs within the membrane. We find that these toxins can partition into membranes under physiologically relevant conditions, but that the toxin–membrane interaction is not sufficient to inhibit Kv channels. From mutagenesis studies we identify regions of the toxin involved in binding to the paddle motif, and those important for interacting with membranes. Modification of membranes with sphingomyelinase D dramatically alters the stability of the toxin–channel complex, suggesting that tarantula toxins interact with paddle motifs within the membrane and that they are sensitive detectors of lipid–channel interactions.

scholarly journals Tarantula toxins use common surfaces for interacting with Kv and ASIC ion channels

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Kanchan Gupta ◽  
Maryam Zamanian ◽  
Chanhyung Bae ◽  
Mirela Milescu ◽  
Dmitriy Krepkiy ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Extracellular Domain ◽  
Voltage Sensor ◽  
Concave Surface ◽  
Voltage Sensing ◽  
Membrane Interaction ◽  
Computational Approaches ◽  
Physical Environments

Tarantula toxins that bind to voltage-sensing domains of voltage-activated ion channels are thought to partition into the membrane and bind to the channel within the bilayer. While no structures of a voltage-sensor toxin bound to a channel have been solved, a structural homolog, psalmotoxin (PcTx1), was recently crystalized in complex with the extracellular domain of an acid sensing ion channel (ASIC). In the present study we use spectroscopic, biophysical and computational approaches to compare membrane interaction properties and channel binding surfaces of PcTx1 with the voltage-sensor toxin guangxitoxin (GxTx-1E). Our results show that both types of tarantula toxins interact with membranes, but that voltage-sensor toxins partition deeper into the bilayer. In addition, our results suggest that tarantula toxins have evolved a similar concave surface for clamping onto α-helices that is effective in aqueous or lipidic physical environments.

scholarly journals Artificial Intelligence, Machine Learning and Deep Learning in Ion Channel Bioinformatics

Membranes ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 672
Author(s):  
Md. Ashrafuzzaman
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Deep Learning ◽  
Ion Channels ◽  
Ion Channel ◽  
Research Trend ◽  
Cellular Processes ◽  
Research Areas ◽  
Huge Data ◽  
Functional Aspects

Ion channels are linked to important cellular processes. For more than half a century, we have been learning various structural and functional aspects of ion channels using biological, physiological, biochemical, and biophysical principles and techniques. In recent days, bioinformaticians and biophysicists having the necessary expertise and interests in computer science techniques including versatile algorithms have started covering a multitude of physiological aspects including especially evolution, mutations, and genomics of functional channels and channel subunits. In these focused research areas, the use of artificial intelligence (AI), machine learning (ML), and deep learning (DL) algorithms and associated models have been found very popular. With the help of available articles and information, this review provide an introduction to this novel research trend. Ion channel understanding is usually made considering the structural and functional perspectives, gating mechanisms, transport properties, channel protein mutations, etc. Focused research on ion channels and related findings over many decades accumulated huge data which may be utilized in a specialized scientific manner to fast conclude pinpointed aspects of channels. AI, ML, and DL techniques and models may appear as helping tools. This review aims at explaining the ways we may use the bioinformatics techniques and thus draw a few lines across the avenue to let the ion channel features appear clearer.

Theory A, Theory B and Theory C of managing people at work

2021 ◽  
Vol 5 (1) ◽  
pp. 69-75
Author(s):  
Birendra Nath Singh
Keyword(s):  
Empirical Studies ◽  
Shop Floor ◽  
Scientific Management ◽  
Business Organization ◽  
Business Organizations ◽  
Research Gaps ◽  
Future Studies ◽  
Modern Business ◽  
And Control ◽  
The Impact

Managing people and productivity are prime concerns of modern business organizations. Many empirical studies were conducted during the era of scientific management (Taylor, 1911) to investigate What and How? McGregor’s (1960) epic theory — Theory X and Theory Y, categorizing all employees into two groups and prescribing methods to motivate and control them was the best. However, his findings also suffered strong criticisms, creating research gaps. The objective of this study was to investigate further and to conclude that there are three major groups named Theory A, Theory B, and Theory C. Amongst them, a middle group — Theory B is most dominant, having all capabilities to significantly influence productivity and prosperity of organizations. The methodology used was qualitative, based upon intensive and critical shop-floor observations. Since this study was not empirical, it had many limitations requiring further researches. Therefore, rightly recommended that future studies should correlate the impact of technological advancements upon motivations and productivity of the modern business organization (Veitch, 2018).

scholarly journals Structural insights into ADP-ribosylation of ubiquitin by Deltex family E3 ubiquitin ligases

2020 ◽  
Vol 6 (38) ◽  
pp. eabc0418
Author(s):  
Chatrin Chatrin ◽  
Mads Gabrielsen ◽  
Lori Buetow ◽  
Mark A. Nakasone ◽  
Syed F. Ahmed ◽  
...  
Keyword(s):  
Cross Talk ◽  
Posttranslational Modifications ◽  
Unknown Function ◽  
Carboxyl Terminus ◽  
Structural Studies ◽  
Future Studies ◽  
Adp Ribosylation ◽  
Carboxyl Terminal ◽  
Adp Ribosyltransferase ◽  
Structural Insights

Cellular cross-talk between ubiquitination and other posttranslational modifications contributes to the regulation of numerous processes. One example is ADP-ribosylation of the carboxyl terminus of ubiquitin by the E3 DTX3L/ADP-ribosyltransferase PARP9 heterodimer, but the mechanism remains elusive. Here, we show that independently of PARP9, the conserved carboxyl-terminal RING and DTC (Deltex carboxyl-terminal) domains of DTX3L and other human Deltex proteins (DTX1 to DTX4) catalyze ADP-ribosylation of ubiquitin’s Gly76. Structural studies reveal a hitherto unknown function of the DTC domain in binding NAD+. Deltex RING domain recruits E2 thioesterified with ubiquitin and juxtaposes it with NAD+ bound to the DTC domain to facilitate ADP-ribosylation of ubiquitin. This ubiquitin modification prevents its activation but is reversed by the linkage nonspecific deubiquitinases. Our study provides mechanistic insights into ADP-ribosylation of ubiquitin by Deltex E3s and will enable future studies directed at understanding the increasingly complex network of ubiquitin cross-talk.

Current status of Plasmodium knowlesi vectors: a public health concern?

Parasitology ◽  
2016 ◽  
Vol 145 (1) ◽  
pp. 32-40 ◽  
Author(s):  
I. VYTHILINGAM ◽  
M. L. WONG ◽  
W. S. WAN-YUSSOF
Keyword(s):  
Public Health ◽  
Plasmodium Knowlesi ◽  
Point Of View ◽  
Control Measures ◽  
Health Concern ◽  
Current Status ◽  
Malaria Vectors ◽  
Future Studies ◽  
Simian Malaria ◽  
And Control

SUMMARYPlasmodium knowlesi a simian malaria parasite is currently affecting humans in Southeast Asia. Malaysia has reported the most number of cases and P. knowlesi is the predominant species occurring in humans. The vectors of P. knowlesi belong to the Leucosphyrus group of Anopheles mosquitoes. These are generally described as forest-dwelling mosquitoes. With deforestation and changes in land-use, some species have become predominant in farms and villages. However, knowledge on the distribution of these vectors in the country is sparse. From a public health point of view it is important to know the vectors, so that risk factors towards knowlesi malaria can be identified and control measures instituted where possible. Here, we review what is known about the knowlesi malaria vectors and ascertain the gaps in knowledge, so that future studies could concentrate on this paucity of data in-order to address this zoonotic problem.

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