Role of Caveolae and Caveolins in Health and Disease

2004 ◽  
Vol 84 (4) ◽  
pp. 1341-1379 ◽  
Author(s):  
Alex W. Cohen ◽  
Robert Hnasko ◽  
William Schubert ◽  
Michael P. Lisanti
Keyword(s):  
Signaling Molecules ◽  
Membrane Lipid ◽  
Scaffolding Proteins ◽  
Cellular Functions ◽  
Coated Pits ◽  
Caveolin 1 ◽  
Plasma Membrane Lipid ◽  
Wide Range ◽  
Health And Disease ◽  
Vesicular Transporters

Although they were discovered more than 50 years ago, caveolae have remained enigmatic plasmalemmal organelles. With their characteristic “flasklike” shape and virtually ubiquitous tissue distribution, these interesting structures have been implicated in a wide range of cellular functions. Similar to clathrin-coated pits, caveolae function as macromolecular vesicular transporters, while their unique lipid composition classifies them as plasma membrane lipid rafts, structures enriched in a variety of signaling molecules. The caveolin proteins (caveolin-1, -2, and -3) serve as the structural components of caveolae, while also functioning as scaffolding proteins, capable of recruiting numerous signaling molecules to caveolae, as well as regulating their activity. That so many signaling molecules and signaling cascades are regulated by an interaction with the caveolins provides a paradigm by which numerous disease processes may be affected by ablation or mutation of these proteins. Indeed, studies in caveolin-deficient mice have implicated these structures in a host of human diseases, including diabetes, cancer, cardiovascular disease, atherosclerosis, pulmonary fibrosis, and a variety of degenerative muscular dystrophies. In this review, we provide an in depth summary regarding the mechanisms by which caveolae and caveolins participate in human disease processes.

scholarly journals METALLOTHIONEINS AS SENSORS AND CONTROLS EXCHANGE OF METALS IN THE CELLS

2014 ◽  
Vol 13 (3) ◽  
pp. 91-99 ◽  
Author(s):  
V. A. Kutyakov ◽  
A. V. Salmina
Keyword(s):  
Stress Factors ◽  
Special Role ◽  
Cellular Functions ◽  
Regulation Of Expression ◽  
Wide Range ◽  
Health And Disease ◽  
Pharmacology And Toxicology ◽  
Regulatory Functions ◽  
The Impact

The basic information on the classification, structure, induction and degradation, functions of the protein family – metallothionein (MT), including CNS in health and disease are presented in this review. It was found that four major isoforms of metallothionein perform different biological roles, are localized in dif- ferent tissues. Induction of MT is a universal reaction to the impact of a variety of stress factors. In recent years, understanding of the role of metallothioneins in metal homeostasis in the tissues in normal and pathological conditions have changed significantly. Notes polyfunctionality metallothioneins (transport of metal ions, maintaining redox reactions, tread, signal, modulated and regulatory functions) and their im- pact on basic cellular functions such as proliferation, differentiation, programmed cell death. Further- more, a special role is shown MT in the pathogenesis of cardiovascular, neurodegenerative and neoplastic disorders.Currently, these molecules are increasingly considered as potential targets for therapy of a wide range of diseases and the development of targeted approaches to the regulation of expression of MT – one of the promising areas of pharmacology and toxicology. Stressed the safety of metallothioneins as therapeutic agents.

scholarly journals Global analysis of protein arginine methylation

2021 ◽  
Author(s):  
Fangrong Zhang ◽  
Jakob Kerbl-Knapp ◽  
Maria J. Rodriguez Colman ◽  
Therese Macher ◽  
Nemanja Vujić ◽  
...  
Keyword(s):  
Global Analysis ◽  
High Sensitivity ◽  
Quantitative Information ◽  
Arginine Methylation ◽  
Cellular Functions ◽  
Physiological Processes ◽  
Mouse Tissues ◽  
Wide Range ◽  
Health And Disease ◽  
Protein Arginine Methylation

SummaryQuantitative information about the levels and dynamics of post-translational modifications (PTMs) is critical for an understanding of cellular functions. Protein arginine methylation (ArgMet) is an important subclass of PTMs and is involved in a plethora of (patho)physiological processes. However, due to the lack of methods for global analysis of ArgMet, the link between ArgMet levels, dynamics and (patho)physiology remains largely unknown. We utilized the high sensitivity and robustness of Nuclear Magnetic Resonance (NMR) spectroscopy to develop a general method for the quantification of global protein ArgMet. Our NMR-based approach enables the detection of protein ArgMet in purified proteins, cells, organoids, and mouse tissues. We demonstrate that the process of ArgMet is a highly prevalent PTM and can be modulated by small-molecule inhibitors and metabolites and changes in cancer and during ageing. Thus, our approach enables to address a wide range of biological questions related to ArgMet in health and disease.Graphical Abstract

scholarly journals Quantifying Mitochondrial Dynamics in Patient Fibroblasts with Multiple Developmental Defects and Mitochondrial Disorders

2021 ◽  
Vol 22 (12) ◽  
pp. 6263
Author(s):  
Ajibola B. Bakare ◽  
Julienne Daniel ◽  
Joshua Stabach ◽  
Anapaula Rojas ◽  
Austin Bell ◽  
...  
Keyword(s):  
Cell Lines ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Disorders ◽  
Cellular Functions ◽  
Developmental Defects ◽  
Mitochondrial Structure ◽  
Wide Range ◽  
Health And Disease ◽  
Diseased State ◽  
Comprehensive Study

Mitochondria are dynamic organelles that undergo rounds of fission and fusion and exhibit a wide range of morphologies that contribute to the regulation of different signaling pathways and various cellular functions. It is important to understand the differences between mitochondrial structure in health and disease so that therapies can be developed to maintain the homeostatic balance of mitochondrial dynamics. Mitochondrial disorders are multisystemic and characterized by complex and variable clinical pathologies. The dynamics of mitochondria in mitochondrial disorders is thus worthy of investigation. Therefore, in this study, we performed a comprehensive analysis of mitochondrial dynamics in ten patient-derived fibroblasts containing different mutations and deletions associated with various mitochondrial disorders. Our results suggest that the most predominant morphological signature for mitochondria in the diseased state is fragmentation, with eight out of the ten cell lines exhibiting characteristics consistent with fragmented mitochondria. To our knowledge, this is the first comprehensive study that quantifies mitochondrial dynamics in cell lines with a wide array of developmental and mitochondrial disorders. A more thorough analysis of the correlations between mitochondrial dynamics, mitochondrial genome perturbations, and bioenergetic dysfunction will aid in identifying unique morphological signatures of various mitochondrial disorders in the future.

scholarly journals Autophagy wins the 2016 Nobel Prize in Physiology or Medicine: Breakthroughs in baker's yeast fuel advances in biomedical research

2016 ◽  
Vol 114 (2) ◽  
pp. 201-205 ◽  
Author(s):  
Beth Levine ◽  
Daniel J. Klionsky
Keyword(s):  
Nobel Prize ◽  
Genotoxic Stress ◽  
Cellular Functions ◽  
Nobel Committee ◽  
Genetic Studies ◽  
Cellular Survival ◽  
Pathogen Elimination ◽  
Wide Range ◽  
Health And Disease ◽  
Key Steps

Autophagy is an ancient pathway in which parts of eukaryotic cells are self-digested within the lysosome or vacuole. This process has been studied for the past seven decades; however, we are only beginning to gain a molecular understanding of the key steps required for autophagy. Originally characterized as a hormonal and starvation response, we now know that autophagy has a much broader role in biology, including organellar remodeling, protein and organelle quality control, prevention of genotoxic stress, tumor suppression, pathogen elimination, regulation of immunity and inflammation, maternal DNA inheritance, metabolism, and cellular survival. Although autophagy is usually a degradative pathway, it also participates in biosynthetic and secretory processes. Given that autophagy has a fundamental role in many essential cellular functions, it is not surprising that autophagic dysfunction is associated with a wide range of human diseases. Genetic studies in various fungi, particularlySaccharomyces cerevisiae, provided the key initial breakthrough that led to an explosion of research on the basic mechanisms and the physiological connections of autophagy to health and disease. The Nobel Committee has recognized this breakthrough by the awarding of the 2016 Nobel Prize in Physiology or Medicine for research in autophagy.

MONTE CARLO STUDY OF LIPID NANOSCALE ORGANIZATION IN CELL MEMBRANES: TUNING DOMAIN SIZE AND STABILITY NEAR THE PHASE BOUNDARY

2009 ◽  
Vol 04 (03) ◽  
pp. 245-265 ◽  
Author(s):  
RAMON REIGADA
Keyword(s):  
Monte Carlo ◽  
Phase Boundary ◽  
Cell Membranes ◽  
Domain Size ◽  
Monte Carlo Study ◽  
Membrane Lipid ◽  
Cellular Functions ◽  
Lipid Mixture ◽  
Wide Range ◽  
Lipid Organization

Lipids in cell membranes are organized in cholesterol-rich domains that are involved in many important cellular functions. Depending on the cell state, such structures are believed to develop covering a wide range of submicrometric sizes and different levels of stability. Using a simple Monte Carlo approach I demonstrate that when the membrane lipid mixture approaches a phase boundary, the cell has several mechanisms to tune both the size and stability of these domains. Cholesterol levels variation, presence of ceramides and insertion of proteins provide plausible mechanisms for the control of the nanoscale lipid organization in cell membranes.

scholarly journals Relationships between EGFR Signaling–competent and Endocytosis-competent Membrane Microdomains

2005 ◽  
Vol 16 (6) ◽  
pp. 2704-2718 ◽  
Author(s):  
Claudia Puri ◽  
Daniela Tosoni ◽  
Riccardo Comai ◽  
Andrea Rabellino ◽  
Daniela Segat ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Egf Receptor ◽  
Membrane Lipid ◽  
Receptor Internalization ◽  
Membrane Microdomains ◽  
Egfr Signaling ◽  
Coated Pits ◽  
Plasma Membrane Lipid ◽  
Epidermal Growth ◽  
Endocytic Proteins

Membrane microdomains, the so-called lipid rafts, function as platforms to concentrate receptors and assemble the signal transduction machinery. Internalization, in most cases, is carried out by different specialized structures, the clathrin-coated pits. Here, we show that several endocytic proteins are efficiently recruited to morphologically identified plasma membrane lipid rafts, upon activation of the epidermal growth factor (EGF) receptor (EGFR), a receptor tyrosine kinase. Analysis of detergent-resistant membrane fractions revealed that the EGF-dependent association of endocytic proteins with rafts is as efficient as that of signaling effector molecules, such as Grb2 or Shc. Finally, the EGFR, but not the nonsignaling transferrin receptor, could be localized in nascent coated pits that almost invariably contained raft membranes. Thus, specialized membrane microdomains have the ability to assemble both the molecular machineries necessary for intracellular propagation of EGFR effector signals and for receptor internalization.

Neuroligin-2 as a central organizer of inhibitory synapses in health and disease

2020 ◽  
Vol 13 (663) ◽  
pp. eabd8379
Author(s):  
Heba Ali ◽  
Lena Marth ◽  
Dilja Krueger-Burg
Keyword(s):  
Synaptic Transmission ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Inhibitory Synapses ◽  
Molecular Architecture ◽  
Cellular Functions ◽  
Altered Expression ◽  
Health And Disease ◽  
Flow Of Information

Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of synaptic adhesion proteins called neuroligins. Neuroligins form transsynaptic bridges with presynaptic neurexins to regulate various aspects of excitatory and inhibitory synaptic transmission. Neuroligin-2 (NLGN2) is the only member that acts exclusively at GABAergic inhibitory synapses. Altered expression and mutations in NLGN2 and several of its interacting partners are linked to cognitive and psychiatric disorders, including schizophrenia, autism, and anxiety. Research on NLGN2 has fundamentally shaped our understanding of the molecular architecture of inhibitory synapses. Here, we discuss the current knowledge on the molecular and cellular functions of mammalian NLGN2 and its role in the neuronal circuitry that regulates behavior in rodents and humans.

scholarly journals Nuclear Envelope Integrity in Health and Disease: Consequences on Genome Instability and Inflammation

2021 ◽  
Vol 22 (14) ◽  
pp. 7281
Author(s):  
Benoit R. Gauthier ◽  
Valentine Comaills
Keyword(s):  
Nuclear Envelope ◽  
Clinical Symptoms ◽  
Genome Instability ◽  
Chromosomal Rearrangements ◽  
Wide Range ◽  
Complex Chromosomal Rearrangements ◽  
Health And Disease ◽  
Dna Release ◽  
Sting Pathway ◽  
Eukaryote Genome

The dynamic nature of the nuclear envelope (NE) is often underestimated. The NE protects, regulates, and organizes the eukaryote genome and adapts to epigenetic changes and to its environment. The NE morphology is characterized by a wide range of diversity and abnormality such as invagination and blebbing, and it is a diagnostic factor for pathologies such as cancer. Recently, the micronuclei, a small nucleus that contains a full chromosome or a fragment thereof, has gained much attention. The NE of micronuclei is prone to collapse, leading to DNA release into the cytoplasm with consequences ranging from the activation of the cGAS/STING pathway, an innate immune response, to the creation of chromosomal instability. The discovery of those mechanisms has revolutionized the understanding of some inflammation-related diseases and the origin of complex chromosomal rearrangements, as observed during the initiation of tumorigenesis. Herein, we will highlight the complexity of the NE biology and discuss the clinical symptoms observed in NE-related diseases. The interplay between innate immunity, genomic instability, and nuclear envelope leakage could be a major focus in future years to explain a wide range of diseases and could lead to new classes of therapeutics.

scholarly journals Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vikas A. Tillu ◽  
James Rae ◽  
Ya Gao ◽  
Nicholas Ariotti ◽  
Matthias Floetenmeyer ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Membrane Lipid ◽  
Membrane Curvature ◽  
Caveolin 1 ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Solution Generation ◽  
Endosomal System ◽  
Disordered Regions

AbstractCaveolae are spherically shaped nanodomains of the plasma membrane, generated by cooperative assembly of caveolin and cavin proteins. Cavins are cytosolic peripheral membrane proteins with negatively charged intrinsically disordered regions that flank positively charged α-helical regions. Here, we show that the three disordered domains of Cavin1 are essential for caveola formation and dynamic trafficking of caveolae. Electrostatic interactions between disordered regions and α-helical regions promote liquid-liquid phase separation behaviour of Cavin1 in vitro, assembly of Cavin1 oligomers in solution, generation of membrane curvature, association with caveolin-1, and Cavin1 recruitment to caveolae in cells. Removal of the first disordered region causes irreversible gel formation in vitro and results in aberrant caveola trafficking through the endosomal system. We propose a model for caveola assembly whereby fuzzy electrostatic interactions between Cavin1 and caveolin-1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.

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