Use of Detergents to Study Membrane Rafts: The Good, the Bad, and the Ugly

2003 ◽  
Vol 384 (9) ◽  
pp. 1259-1263 ◽  
Author(s):  
H. Shogomori ◽  
D.A. Brown
Keyword(s):  
Lipid Rafts ◽  
Cell Membranes ◽  
Eukaryotic Cell ◽  
Membrane Rafts ◽  
Ionic Detergents ◽  
Wide Range ◽  
Range Of Functions ◽  
Acyl Chains

Abstract Eukaryotic cell membranes contain microdomains called lipid rafts, which are cholesterol-rich domains in which lipid acyl chains are tightly packed and highly extended. A variety of proteins associate preferentially with rafts, and this raft association is important in a wide range of functions. A powerful and widely used method for studying lipid rafts takes advantage of their insolubility in non-ionic detergents. Here we describe the basis of detergent insolubility, and review strengths, limitations, and unresolved puzzles regarding this method.

scholarly journals Primary cilia and lipid raft dynamics

Open Biology ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 210130
Author(s):  
Yuhei Nishimura ◽  
Daishi Yamakawa ◽  
Katsunori Uchida ◽  
Takashi Shiromizu ◽  
Masatoshi Watanabe ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Cancer Biology ◽  
Primary Cilia ◽  
Membrane Microdomains ◽  
Wide Range ◽  
Range Of Functions ◽  
Specific Proteins ◽  
The Relationship

Primary cilia, antenna-like structures of the plasma membrane, detect various extracellular cues and transduce signals into the cell to regulate a wide range of functions. Lipid rafts, plasma membrane microdomains enriched in cholesterol, sphingolipids and specific proteins, are also signalling hubs involved in a myriad of physiological functions. Although impairment of primary cilia and lipid rafts is associated with various diseases, the relationship between primary cilia and lipid rafts is poorly understood. Here, we review a newly discovered interaction between primary cilia and lipid raft dynamics that occurs during Akt signalling in adipogenesis. We also discuss the relationship between primary cilia and lipid raft-mediated Akt signalling in cancer biology. This review provides a novel perspective on primary cilia in the regulation of lipid raft dynamics.

664: CXCL12/CXCR4 Trans-Activation of HER2 in Lipid Rafts of Prostate Cancer Cell Membranes Promotes Bone Metastasis

2007 ◽  
Vol 177 (4S) ◽  
pp. 223-223
Author(s):  
Sreenivasa R. Chinni ◽  
Hamilto Yamamoto ◽  
Zhong Dong ◽  
Aaron Sabbota ◽  
Sanaa Nabha ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Lipid Rafts ◽  
Cancer Cell ◽  
Cell Membranes ◽  
Prostate Cancer Cell

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

scholarly journals Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook

2021 ◽  
Vol 22 (5) ◽  
pp. 2754
Author(s):  
Naila Qayyum ◽  
Muhammad Haseeb ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Signaling Complex ◽  
Current Review ◽  
Wide Range ◽  
Range Of Functions ◽  
Species Production ◽  
And Oxidative Stress ◽  
Significant Attention

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.

scholarly journals The Role of HCN Channels on Membrane Excitability in the Nervous System

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Daisuke Kase ◽  
Keiji Imoto
Keyword(s):  
Intracellular Signaling ◽  
Hcn Channels ◽  
Heart Cells ◽  
Hcn Channel ◽  
Membrane Excitability ◽  
Wide Range ◽  
Inward Currents ◽  
Range Of Functions ◽  
Channel Currents

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP2, and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons.

scholarly journals Secondary Structure Libraries for Artificial Evolution Experiments

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1671
Author(s):  
Ráchel Sgallová ◽  
Edward A. Curtis
Keyword(s):  
Secondary Structure ◽  
Sequence Space ◽  
In Vitro Selection ◽  
Random Sequence ◽  
Random Mutagenesis ◽  
Nucleotide Composition ◽  
Artificial Evolution ◽  
Wide Range ◽  
Range Of Functions

Methods of artificial evolution such as SELEX and in vitro selection have made it possible to isolate RNA and DNA motifs with a wide range of functions from large random sequence libraries. Once the primary sequence of a functional motif is known, the sequence space around it can be comprehensively explored using a combination of random mutagenesis and selection. However, methods to explore the sequence space of a secondary structure are not as well characterized. Here we address this question by describing a method to construct libraries in a single synthesis which are enriched for sequences with the potential to form a specific secondary structure, such as that of an aptamer, ribozyme, or deoxyribozyme. Although interactions such as base pairs cannot be encoded in a library using conventional DNA synthesizers, it is possible to modulate the probability that two positions will have the potential to pair by biasing the nucleotide composition at these positions. Here we show how to maximize this probability for each of the possible ways to encode a pair (in this study defined as A-U or U-A or C-G or G-C or G.U or U.G). We then use these optimized coding schemes to calculate the number of different variants of model stems and secondary structures expected to occur in a library for a series of structures in which the number of pairs and the extent of conservation of unpaired positions is systematically varied. Our calculations reveal a tradeoff between maximizing the probability of forming a pair and maximizing the number of possible variants of a desired secondary structure that can occur in the library. They also indicate that the optimal coding strategy for a library depends on the complexity of the motif being characterized. Because this approach provides a simple way to generate libraries enriched for sequences with the potential to form a specific secondary structure, we anticipate that it should be useful for the optimization and structural characterization of functional nucleic acid motifs.

Secretory Proteases of the Human Skin Microbiome

2021 ◽  
Author(s):  
Wisely Chua ◽  
Si En Poh ◽  
Hao Li
Keyword(s):  
Human Skin ◽  
Hydrolytic Enzymes ◽  
Microbial Interactions ◽  
Skin Microbiome ◽  
Protein Cleavage ◽  
Wide Range ◽  
Range Of Functions ◽  
Diverse Community ◽  
Secreted Proteases ◽  
Pathogenic Agents

The human skin is our outermost layer and serves as a protective barrier against external insults. Advances in next generation sequencing have enabled the discoveries of a rich and diverse community of microbes - bacteria, fungi and viruses that are residents of this surface. The genomes of these microbes also revealed the presence of many secretory enzymes. In particular, proteases which are hydrolytic enzymes capable of protein cleavage and degradation are of special interest in the skin environment which is enriched in proteins and lipids. In this minireview, we will focus on the roles of these skin-relevant microbial secreted proteases, both in terms of their widely studied roles as pathogenic agents in tissue invasion and host immune inactivation, and their recently discovered roles in inter-microbial interactions and modulation of virulence factors. From these studies, it has become apparent that while microbial proteases are capable of a wide range of functions, their expression is tightly regulated and highly responsive to the environments the microbes are in. With the introduction of new biochemical and bioinformatics tools to study protease functions, it will be important to understand the roles played by skin microbial secretory proteases in cutaneous health, especially the less studied commensal microbes with an emphasis on contextual relevance.

The thermodynamic properties of mixed phospholipid bilayers: a theoretical analysis

1984 ◽  
Vol 62 (8) ◽  
pp. 796-802 ◽  
Author(s):  
Maryse Mondat ◽  
A. Georgallas ◽  
D. A. Pink ◽  
M. J. Zuckermann
Keyword(s):  
Experimental Data ◽  
Thermodynamic Properties ◽  
Reasonable Agreement ◽  
Phospholipid Bilayers ◽  
Scanning Calorimetry ◽  
Phase Separations ◽  
Lipid Mixtures ◽  
Wide Range ◽  
Acyl Chains ◽  
Gel Phase

A theoretical model is presented with the intention of describing lateral phase separations in binary lipid mixtures in which the acyl chains of the components differ in their length. The model includes explicitly interactions between the acyl chains and between polar heads of the lipid molecules. Phase diagrams and thermodynamic properties of binary lipid mixtures were calculated using a wide range of interaction parameters. It is shown that the occurrence of immiscibility in the gel phase is related to the interactions between the polar heads of the lipid molecules. The calculated results for binary lipid mixtures are compared with the available experimental data. In particular, the calculated specific heat for dilauroyl phosphatidylcholine – distearoyl phosphatidylcholine is in reasonable agreement with experimental results obtained from differential scanning calorimetry measurements.

scholarly journals Ultrabithorax Is a Micromanager of Hindwing Identity in Butterflies and Moths

2021 ◽  
Vol 9 ◽  
Author(s):  
Amruta Tendolkar ◽  
Aaron F. Pomerantz ◽  
Christa Heryanto ◽  
Paul D. Shirk ◽  
Nipam H. Patel ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Targeted Mutagenesis ◽  
Junonia Coenia ◽  
Wing Venation ◽  
Loss Of Function ◽  
Color Patterns ◽  
Wide Range ◽  
Range Of Functions ◽  
Gene Regulatory ◽  
Pyralid Moth

The forewings and hindwings of butterflies and moths (Lepidoptera) are differentiated from each other, with segment-specific morphologies and color patterns that mediate a wide range of functions in flight, signaling, and protection. The Hox gene Ultrabithorax (Ubx) is a master selector gene that differentiates metathoracic from mesothoracic identities across winged insects, and previous work has shown this role extends to at least some of the color patterns from the butterfly hindwing. Here we used CRISPR targeted mutagenesis to generate Ubx loss-of-function somatic mutations in two nymphalid butterflies (Junonia coenia, Vanessa cardui) and a pyralid moth (Plodia interpunctella). The resulting mosaic clones yielded hindwing-to-forewing transformations, showing Ubx is necessary for specifying many aspects of hindwing-specific identities, including scale morphologies, color patterns, and wing venation and structure. These homeotic phenotypes showed cell-autonomous, sharp transitions between mutant and non-mutant scales, except for clones that encroached into the border ocelli (eyespots) and resulted in composite and non-autonomous effects on eyespot ring determination. In the pyralid moth, homeotic clones converted the folding and depigmented hindwing into rigid and pigmented composites, affected the wing-coupling frenulum, and induced ectopic scent-scales in male androconia. These data confirm Ubx is a master selector of lepidopteran hindwing identity and suggest it acts on many gene regulatory networks involved in wing development and patterning.

scholarly journals Distinct roles for innexin gap junctions and hemichannels in mechanosensation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Denise S Walker ◽  
William R Schafer
Keyword(s):  
Blood Pressure ◽  
Heterologous Expression ◽  
Pain Perception ◽  
Mechanosensory Transduction ◽  
Wide Range ◽  
Touch Receptor Neurons ◽  
Touch Sensitivity ◽  
Range Of Functions ◽  
Receptor Neurons ◽  
And Control

Mechanosensation is central to a wide range of functions, including tactile and pain perception, hearing, proprioception, and control of blood pressure, but identifying the molecules underlying mechanotransduction has proved challenging. In Caenorhabditis elegans, the avoidance response to gentle body touch is mediated by six touch receptor neurons (TRNs), and is dependent on MEC-4, a DEG/ENaC channel. We show that hemichannels containing the innexin protein UNC-7 are also essential for gentle touch in the TRNs, as well as harsh touch in both the TRNs and the PVD nociceptors. UNC-7 and MEC-4 do not colocalize, suggesting that their roles in mechanosensory transduction are independent. Heterologous expression of unc-7 in touch-insensitive chemosensory neurons confers ectopic touch sensitivity, indicating a specific role for UNC-7 hemichannels in mechanosensation. The unc-7 touch defect can be rescued by the homologous mouse gene Panx1 gene, thus, innexin/pannexin proteins may play broadly conserved roles in neuronal mechanotransduction.

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