Clathrin Light Chains: Not to Be Taken so Lightly

Clathrin is a cytosolic protein involved in the intracellular trafficking of a wide range of cargo. It is composed of three heavy chains and three light chains that together form a triskelion, the subunit that polymerizes to form a clathrin coated vesicle. In addition to its role in membrane trafficking, clathrin is also involved in various cellular and biological processes such as chromosomal segregation during mitosis and organelle biogenesis. Although the role of the heavy chains in regulating important physiological processes has been well documented, we still lack a complete understanding of how clathrin light chains regulate membrane traffic and cell signaling. This review highlights the importance and contributions of clathrin light chains in regulating clathrin assembly, vesicle formation, endocytosis of selective receptors and physiological and developmental processes.

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The Role of Metal Regulatory Proteins in Brain Oxidative Stress: A Tutorial

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/981561 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Wayne Briner

Keyword(s):

Oxidative Stress ◽

Redox Activity ◽

Biological Processes ◽

Physiological Processes ◽

Pharmacological Targets ◽

Wide Range ◽

Brain Oxidative Stress ◽

The Brain ◽

And Oxidative Stress

The proteins that regulate the metabolism of a metal must also play a role in regulating the redox activity of the metal. Metals are intrinsic to a substantial number of biological processes and the proteins that regulate those activities are also considerable in number. The role these proteins play in a wide range of physiological processes involves them directly and indirectly in a variety of disease processes. Similarly, it may be therapeutically advantageous to pharmacologically alter the activity of these metal containing proteins to influence disease processes. This paper will introduce the reader to a number of important proteins in both metal metabolism and oxidative stress, with an emphasis on the brain. Potential pharmacological targets will be considered.

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Role of Insulin in Health and Disease: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms22126403 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6403

Author(s):

Md Saidur Rahman ◽

Khandkar Shaharina Hossain ◽

Sharnali Das ◽

Sushmita Kundu ◽

Elikanah Olusayo Adegoke ◽

...

Keyword(s):

Insulin Signaling ◽

Basic Research ◽

Future Research ◽

Protective Effects ◽

Glucose Levels ◽

Physiological Processes ◽

Blood Glucose Levels ◽

Wide Range ◽

Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

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Spatiotemporal Control of Intracellular Membrane Trafficking by Rho GTPases

Cells ◽

10.3390/cells8121478 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1478 ◽

Cited By ~ 3

Author(s):

Monilola A. Olayioye ◽

Bettina Noll ◽

Angelika Hausser

Keyword(s):

Membrane Trafficking ◽

Rho Gtpases ◽

Rho Gtpase ◽

Regulatory Proteins ◽

Biological Processes ◽

Intracellular Membrane ◽

Master Regulators ◽

Cytoskeletal Remodeling ◽

Wide Range ◽

Spatiotemporal Control

As membrane-associated master regulators of cytoskeletal remodeling, Rho GTPases coordinate a wide range of biological processes such as cell adhesion, motility, and polarity. In the last years, Rho GTPases have also been recognized to control intracellular membrane sorting and trafficking steps directly; however, how Rho GTPase signaling is regulated at endomembranes is still poorly understood. In this review, we will specifically address the local Rho GTPase pools coordinating intracellular membrane trafficking with a focus on the endo- and exocytic pathways. We will further highlight the spatiotemporal molecular regulation of Rho signaling at endomembrane sites through Rho regulatory proteins, the GEFs and GAPs. Finally, we will discuss the contribution of dysregulated Rho signaling emanating from endomembranes to the development and progression of cancer.

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The role of Galactose in human health and disease

Open Medicine ◽

10.2478/s11536-012-0022-z ◽

2012 ◽

Vol 7 (4) ◽

pp. 409-419 ◽

Cited By ~ 4

Author(s):

Muhammad Manwar Hussain ◽

Mukhtarul Hassan ◽

Noor Shaik ◽

Zeeshan Iqbal

Keyword(s):

Human Health ◽

Cellular Signaling ◽

Biological Processes ◽

Microbial Adhesion ◽

Wide Range ◽

Health And Disease ◽

Stereochemical Properties ◽

Specific Sugar

AbstractAccording to the universal biological findings, cellular bodies are covered with an intense coating of glycans. Diversity of glycan chains, linked to lipids and proteins is due to isomeric and conformational modifications of various sugar residues, giving rise to unique carbohydrate structures with a wide range of sequences and anomeric configurations. Proteins and lipids, carrying specific sugar residues (like Galactose) with particular stereochemical properties (sequence, anomery and linkages) are involved in broad spectrums of biological processes, including intercellular and intracellular interactions, microbial adhesion and cellular signaling. By studying the role of specific seterochemical features of galactose (Gal), we have improved our understanding about the normal physiology and diseases in human bodies.

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The universal mechanism of intermediate filament transport

10.1101/251405 ◽

2018 ◽

Author(s):

Amélie Robert ◽

Peirun Tian ◽

Stephen A. Adam ◽

Robert D. Goldman ◽

Vladimir I. Gelfand

Keyword(s):

Cell Shape ◽

Actin Dynamics ◽

Light Chains ◽

Unexpected Result ◽

Motile Cells ◽

Physiological Properties ◽

Wide Range ◽

Keratin Filament ◽

Universal Mechanism

ABSTRACTIntermediate filaments (IFs) are a major component of the cytoskeleton that regulates a wide range of physiological properties in eukaryotic cells. In motile cells, the IF network has to adapt to constant changes of cell shape and tension. In this study, we used two cell lines that express vimentin and keratins 8/18 to study the dynamic behavior of these IFs. We demonstrated that both IF types undergo extensive transport along microtubules. This was an unexpected result as keratin filament remodeling has been described to depend on actin dynamics. We established the role of kinesin-1 in vimentin and keratin IF transport by knocking out KIF5B, the ubiquitous isoform of kinesin-1. Futhermore, we demonstrated that unlike typical membrane cargoes, transport of both types of IFs does not involve kinesin light chains, but requires the presence of the same region of the kinesin-1 tail, suggesting a unified mechanism of IF transport.

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WC-1 and the Proximal GATA Sequence Mediate a Cis-/Trans-Acting Repressive Regulation of Light-Dependent Gene Transcription in the Dark

International Journal of Molecular Sciences ◽

10.3390/ijms20122854 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2854 ◽

Cited By ~ 1

Author(s):

Andrea Brenna ◽

Claudio Talora

Keyword(s):

Transcriptional Activation ◽

Dark Light ◽

Consensus Sequences ◽

Physiological Processes ◽

Photo Sensor ◽

Wide Range ◽

White Collar Complex ◽

Light Stimuli ◽

Nucleotide Repeats

Light influences a wide range of physiological processes from prokaryotes to mammals. Neurospora crassa represents an important model system used for studying this signal pathway. At molecular levels, the WHITE COLLAR Complex (WCC), a heterodimer formed by WC-1 (the blue light photo-sensor) and WC-2 (the transcriptional activator), is the critical positive regulator of light-dependent gene expression. GATN (N indicates any other nucleotide) repeats are consensus sequences within the promoters of light-dependent genes recognized by the WCC. The distal GATN is also known as C-box since it is involved in the circadian clock. However, we know very little about the role of the proximal GATN, and the molecular mechanism that controls the transcription of light-induced genes during the dark/light transition it is still unclear. Here we showed a first indication that mutagenesis of the proximal GATA sequence within the target promoter of the albino-3 gene or deletion of the WC-1 zinc finger domain led to a rise in expression of light-dependent genes already in the dark, effectively decoupling light stimuli and transcriptional activation. This is the first observation of cis-/trans-acting repressive machinery, which is not consistent with the light-dependent regulatory mechanism observed in the eukaryotic world so far.

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The roles of grouper clathrin light chains in regulating the infection of a novel marine DNA virus, Singapore grouper iridovirus

Scientific Reports ◽

10.1038/s41598-019-51725-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Liqun Wang ◽

Qiang Li ◽

Songwei Ni ◽

Youhua Huang ◽

Jingguang Wei ◽

...

Keyword(s):

Virus Infection ◽

Light Chains ◽

Dna Virus ◽

Virus Attachment ◽

Heavy Chains ◽

Fish Virus ◽

Early Endosomes ◽

Epinephelus Akaara ◽

First Time

Abstract Clathrins, composed of clathrin heavy chains (CHCs) and clathrin light chains (CLCs), are usually hijacked by viruses for infection. However, the role of CLCs, especially in regulating fish virus infection, remains poorly understood. Here, two isoforms of CLCs were cloned from the red-spotted grouper (Epinephelus akaara) (EaCLCa and EaCLCb). Both EaCLC transcripts were expressed in all examined tissues, and the expression of EaCLCa was much higher than that of EaCLCb. Over-expressing EaCLCa-W119R mutant significantly reduced Singapore grouper iridovirus (SGIV) infectivity. However, no effect of EaCLCb-W122R on SGIV infection was observed. The detailed steps were further studied, mainly including virus attachment, entry and the following transport to early endosomes. EaCLCa-W119R mutant notably inhibited internalization of SGIV particles with no effect on SGIV attachment. Furthermore, EaCLCa-W119R mutant obviously impaired the delivery of SGIV to early endosomes after virus internalization. In addition, the EaCLCa-W119R mutant markedly reduced the colocalization of SGIV and actin. However, EaCLCb is not required for such events during SGIV infection. Taken together, these results demonstrate for the first time that EaCLCa and EaCLCb exerted different impacts on iridovirus infection, providing a better understanding of the mechanisms of SGIV infection and opportunities for the design of new antiviral strategies.

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A comprehensive overview of PPM1A: From structure to disease

Experimental Biology and Medicine ◽

10.1177/15353702211061883 ◽

2021 ◽

pp. 153537022110618

Author(s):

Mao Li ◽

Xingfeng Xu ◽

Yan Su ◽

Xiaoyun Shao ◽

Yali Zhou ◽

...

Keyword(s):

Negative Regulator ◽

Comprehensive Overview ◽

Physiological Processes ◽

Stress Response Pathway ◽

Family Protein ◽

Wide Range ◽

Proliferation And Apoptosis ◽

Insight Into ◽

Phosphate Groups

PPM1A (magnesium-dependent phosphatase 1 A, also known as PP2Cα) is a member of the Ser/Thr protein phosphatase family. Protein phosphatases catalyze the removal of phosphate groups from proteins via hydrolysis, thus opposing the role of protein kinases. The PP2C family is generally considered a negative regulator in the eukaryotic stress response pathway. PPM1A can bind and dephosphorylate various proteins and is therefore involved in the regulation of a wide range of physiological processes. It plays a crucial role in transcriptional regulation, cell proliferation, and apoptosis and has been suggested to be closely related to the occurrence and development of cancers of the lung, bladder, and breast, amongst others. Moreover, it is closely related to certain autoimmune diseases and neurodegenerative diseases. In this review, we provide an insight into currently available knowledge of PPM1A, including its structure, biological function, involvement in signaling pathways, and association with diseases. Lastly, we discuss whether PPM1A could be targeted for therapy of certain human conditions.

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Structural Studies of Dynamin Tubular Crystals by Cryo-Electron Microscopy

Microscopy and Microanalysis ◽

10.1017/s1431927600018444 ◽

1999 ◽

Vol 5 (S2) ◽

pp. 1024-1025

Author(s):

Peijun Zhang ◽

Jenny E. Hinshaw

Keyword(s):

Plasma Membrane ◽

Membrane Trafficking ◽

Lipid Vesicles ◽

Coated Vesicle ◽

Permissive Temperature ◽

Coated Pits ◽

Unique Role ◽

Cryo Electron Microscopy ◽

Tubular Crystals

Dynamin is a 100 kD GTPase that plays an essential role in clathrin-coated vesicle formation during receptor mediated endocytosis, and in caveolae internalization and may play a role in intracellular membrane trafficking (1). It shares an extensive sequence homology (70% identity) to shibiregene product in Drosophila(2,3). The shibiretsmutants exhibit a rapid and reversible paralysis at non-permissive temperature due to a depletion of synaptic vesicles in their nerve termini which is believed to be caused by a block in endocytosis since there is an accumulation of “collared” clathrin-coated pits at the plasma membrane (4). Synaptosomes treated with GTPγs produces elongated necks surrounded by dynamin (6). Purified recombinant dynamin itself can assemble to form spirals and bind to lipid vesicles to form tubes, which resemble the “collar” at the necks of coated pits (5). These dynamin tubes vesiculate upon GTP treatment (7), suggesting a unique role of dynamin acting as a mechanoenzyme which causes clathrin-coated vesicles to be pinched off plasma membrane.

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Activity and Trafficking of Copper-Transporting ATPases in Tumor Development and Defense against Platinum-Based Drugs

Cells ◽

10.3390/cells8091080 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1080 ◽

Cited By ~ 13

Author(s):

Raffaella Petruzzelli ◽

Roman S. Polishchuk

Keyword(s):

Tumor Cells ◽

Membrane Trafficking ◽

Tumor Development ◽

Current Data ◽

Malignant Cells ◽

Potential Toxicity ◽

Cellular Processes ◽

Wide Range ◽

Cu Homeostasis

Membrane trafficking pathways emanating from the Golgi regulate a wide range of cellular processes. One of these is the maintenance of copper (Cu) homeostasis operated by the Golgi-localized Cu-transporting ATPases ATP7A and ATP7B. At the Golgi, these proteins supply Cu to newly synthesized enzymes which use this metal as a cofactor to catalyze a number of vitally important biochemical reactions. However, in response to elevated Cu, the Golgi exports ATP7A/B to post-Golgi sites where they promote sequestration and efflux of excess Cu to limit its potential toxicity. Growing tumors actively consume Cu and employ ATP7A/B to regulate the availability of this metal for oncogenic enzymes such as LOX and LOX-like proteins, which confer higher invasiveness to malignant cells. Furthermore, ATP7A/B activity and trafficking allow tumor cells to detoxify platinum (Pt)-based drugs (like cisplatin), which are used for the chemotherapy of different solid tumors. Despite these noted activities of ATP7A/B that favor oncogenic processes, the mechanisms that regulate the expression and trafficking of Cu ATPases in malignant cells are far from being completely understood. This review summarizes current data on the role of ATP7A/B in the regulation of Cu and Pt metabolism in malignant cells and outlines questions and challenges that should be addressed to understand how ATP7A and ATP7B trafficking mechanisms might be targeted to counteract tumor development.

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