Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells

Volume 2 (2018)

Cover: This month in Cell Stress: Kinase signaling in the innate immune system. Fluorescence microscopic depiction of immune cell responses within the CNS upon chronic pain. Images by Centre for Nanoscale BioPhotonics (CNBP) licensed under the CC BY 2.0 license. Image modified by Cell Stress. The cover is published under the CC BY 4.0 license.

Mitochondrial stress management: a dynamic journey

Miriam Valera-Alberni1,2 and Carles Canto1

Mitochondria undergo continuous challenges in the course of their life, from their generation to their degradation. These challenges include the management of reactive oxygen species, the proper assembly of mitochondrial respiratory complexes and the need to balance potential mutations in the mitochondrial DNA. The detection of damage and the ability to keep it under control is critical to fine-tune mitochondrial function to the organismal energy needs. In this review, we will analyze the multiple mechanisms that safeguard mitochondrial function in light of in crescendo damage. This sequence of events will include initial defense against excessive reactive oxygen species production, compensation mechanisms by the unfolded protein response (UPRmt), mitochondrial dynamics and elimination by mitophagy.

Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets

Konstantin Stoletov1, Lian Willetts1, Perrin H. Beatty1 and John D. Lewis1

INTRODUCTION Currently, many cancer patients undergo chemotherapy, which is aimed at mitigating the risk of future metastasis. These treatments, however, have numerous system-wide off-target effects that negatively impact the patients’

Therapeutic anti-tumor immunity directed against neo-epitopes by intratumor delivery of mRNA encoding MLKL

Lien Van Hoecke1,2 and Xavier Saelens1,2,3

We have developed a potentially generic treatment method to induce tumor antigen-specific cellular immunity based on the transient intra-tumor expression of the necroptosis-inducing factor MLKL (Figure 1). Importantly, we have

Astrocytes, emerging stars of energy homeostasis

Simonetta Camandola1

INTRODUCTION The brain is the organ responsible for the centralized control of the other organs’ functions and, in higher vertebrates, of reasoning. Such tasks are achieved thanks to the interconnections

Base editors: a powerful tool for generating animal models of human diseases

Zongyang Lu1,2 and Xingxu Huang1,3

BASE EDITORS: A NOVEL GENOME ENGINEERING TOOL Genetically engineered mouse models of human diseases have long been used in understanding the underlying mechanisms of the clinically relevant genetic disorders. In

Unweaving the role of nuclear Lamins in neural circuit integrity

Samantha L. Deal1 and Shinya Yamamoto1,2,3,4

Structural integrity of the nuclear membrane is essential for the homeostasis of eukaryotic cells. Critical components of this process are Lamins or type-V intermediate filament proteins that form a meshwork

Red blood cell extracellular vesicles as robust carriers of RNA-based therapeutics

Chanh Tin Pham1, Xin Zhang1, Austin Lam1, Minh TN Le1

The emerging RNA-based therapeutics are renowned for a wide array of druggable targets, which are difficult to achieve by conventional therapies, with high specificity and great versatility. RNA-based drugs function

New insights into the role of soluble E-cadherin in tumor angiogenesis

Maggie K.S. Tang1, Philip P. Ip2 and Alice S.T. Wong1

Ovarian cancer, the leading cause of death among all gynecological malignancies, is a highly aggressive disease with a propensity for metastasis. Due to the discreet anatomical location, by the time

Neuronal Lamin regulates motor circuit integrity and controls motor function and lifespan

Lisa J. Oyston1,2,3, Yong Qi Lin1, Thang M. Khuong1, Qiao-Ping Wang1, Man Tat Lau1, Teleri Clark1 and G. Gregory Neely1

Neuronal aging involves a progressive decline in cognitive abilities and loss of motor function. Mutations in human Lamin genes (LMNA, LMNB1, LMNB2) lead to a wide-range of diseases including muscular dystrophy, peripheral neuropathy and progeria. Here we investigate the role of neuronal Lamin in regulating age-related phenotypes. Neuronal targeting of Lamin led to shortened lifespan, progressive impairment of motor function and loss of dopaminergic (DA) neurons within the protocerebral anterior medial (PAM) cluster in the Drosophila melanogaster brain. Loss of neuronal Lamin caused an age-related decline in neural physiology, with slower neurotransmission and increased chance of motor circuit failure with age. Unexpectedly, Lamin-dependent decline in motor function was specific for the chemical synapses of the dorsal longitudinal muscle (DLM). Together (...)

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Foie gras and liver regeneration: a fat dilemma

Maria Agnese Della Fazia1 and Giuseppe Servillo1

The liver has a unique ability of regenerating after injuries or partial loss of its mass. The mechanisms responsible for liver regeneration – mostly occurring when the hepatic tissue is damaged or functionally compromised by metabolic stress – have been studied in considerable detail over the last few decades, because this phenomenon has both basic-biology and clinical relevance. More specifically, recent interest has been focusing on the widespread occurrence of abnormal nutritional habits in the Western world that result in an increased prevalence of non-alcoholic fatty liver disease (NAFLD). NAFLD is closely associated with insulin resistance and dyslipidemia, and it represents a major clinical challenge. The disease may progress to steatohepatitis with persistent inflammation and progressive liver damage, both of which will compromise regeneration under conditions of partial hepatectomy in surgical oncology or in liver transplantation procedures. Here, we analyze the impact of ER stress and SIRT1 in lipid metabolism and in fatty liver pathology (...)

Amelioration of obesity-induced diabetes by a novel autophagy enhancer

Hyejin Lim1 and Myung-Shik Lee1

Our screening system was a convenient high throughput assay of autophagic flux rather than cumulative autophagy levels, and the index of autophagic activity was calculated as the ratio of the

Epigenetic mechanisms behind cellular sensitivity to DNA damage

Amanda K. Williamson1, Zijing Zhu1 and Zhi-Min Yuan1

INTRODUCTION Epigenetics is the regulation of gene expression independent of the gene sequence itself via the interactions between DNA and proteins called histones [cite]10.4161/epi.24042[/cite]. In the nucleus, DNA is highly

Membrane closure in stress induced-autophagosome formation

Eiji Morita1

Autophagy (macroautophagy) is a bulk degradation system that sequesters cytoplasmic components by generating double-layered isolation membranes and delivering these isolated contents to the lysosomes [cite]10.1146/annurev-cellbio-092910-154005[/cite]. Though this pathway was originally

Striatal dual cholinergic /GABAergic transmission in Parkinson disease: friends or foes?

Natalia Lozovaya1, Yehezkel Ben-Ari1 and Constance Hammond1

Although constituting less than 1% of neuronal population of the striatum, cholinergic interneurons play a major role in the control of sensory integration in preparation for movements. These giant neurons

The NLRC4 inflammasome requires IRF8-dependent production of NAIPs

Ein Lee1,2, Rajendra Karki1 and Thirumala-Devi Kanneganti1

Inflammasomes orchestrate cellular responses to pathogen- or danger-associated molecular patterns by controlling the activation of caspase-1. Inflammasome activation results in enzymatically active caspase-1, which mediates the maturation and release of

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Endolysosomal dysfunction and exosome secretion: implications for neurodegenerative disorders

André M. Miranda1,2,3,4 and Gilbert Di Paolo1,2,5

A master regulator of both endolysosomal function and autophagy is Vps34 and its lipid product phosphatidylinositol-3-phosphate (PI3P) through which the lipid kinase exerts most of its biological actions in eukaryotic

Putting together and taking apart: assembly and disassembly of the Rad51 nucleoprotein filament in DNA repair and genome stability

Tadas Andriuskevicius1, Oleksii Kotenko1 and Svetlana Makovets1

Homologous recombination is a key mechanism providing both genome stability and genetic diversity in all living organisms. Recombinases play a central role in this pathway: multiple protein subunits of Rad51 or its orthologues bind single-stranded DNA to form a nucleoprotein filament which is essential for initiating recombination events. Multiple factors are involved in the regulation of this step, both positively and negatively. In this review, we discuss Rad51 nucleoprotein assembly and disassembly, how it is regulated and what functional significance it has in genome maintenance.

Oxidation of p62 as an evolutionary adaptation to promote autophagy in stress conditions

Elsje G. Otten1,§, Rhoda Stefanatos1, Bernadette Carroll1, Viktor I. Korolchuk1

Autophagy (literally meaning self-eating) is an intracellular trafficking pathway. It involves the formation of a double membraned organelle (called the autophagosome) around components of the cell, such as damaged proteins,

New insights into the key role of HIF-1α in IL-10-producing B cells

Xianyi Meng1, Aline Bozec1

HIFs are heterodimeric transcription factors, consisting of an oxygen-labile alpha subunit (HIF- α) and a constitutively-stable beta subunit (HIF-β), that exert pivotal roles in inducing cellular responses to hypoxia. HIF-1α

How to use a multipurpose SNARE: The emerging role of Snap29 in cellular health

Valeria Mastrodonato1,#, Elena Morelli1,#  and Thomas Vaccari1

[table id=90 /] INTRODUCTION The specialized trafficking routes that evolved between compartments of the endomembrane system rely on a wide set of proteins, including primarily SNAREs, Rab GTPases and a

Therapeutic potential of DNA methyltransferase inhibitors with immune checkpoint inhibitor therapy in breast cancer

Na Luo1, Ayaka Sugiura2 and Justin M. Balko1,3,4,5

Tumor infiltrating lymphocytes (TILs) are a positive prognostic biomarker in breast cancer, particularly in hormone receptor-negative disease. High TILs associate with an improved survival rate in breast cancer patients, and

The emerging role of minor intron splicing in neurological disorders

Daniel Jutzi 1,2,+, Maureen V. Akinyi 3,+, Jonas Mechtersheimer1,2,+, Mikko J. Frilander3 and Marc-David Ruepp1,4

INTRODUCTION Pre-mRNA splicing is an essential step in eukaryotic gene expression. It is predominantly a co-transcriptional process during which the non-coding introns are excised from precursor mRNA (pre-mRNA) molecules and

A new way to regulate inflammation: selective autophagic degradation of IKKγ mediated by ANGPTL8

Yu Zhang1, Ling Zheng2 and Kun Huang1

Activation of transcription factor nuclear factor-κB (NF-κB) is one of the central events in inflammation and immunity. In resting cells, the activity of NF-κB is inhibited by its binding partner,

Rejuvenation of the aged neuromuscular junction by exercise

Tabita Kreko-Pierce1,2 and Benjamin A. Eaton1,2

Age-dependent declines in muscle function are observed across species. The loss of mobility resulting from the decline in muscle function represents an important health issue and a key determinant of quality of life for the elderly. It is believed that changes in the structure and function of the neuromuscular junction are important contributors to the observed declines in motor function with increased age. Numerous studies indicate that the aging muscle is an important contributor to the deterioration of the neuromuscular junction but the cellular and molecular mechanisms driving the degeneration of the synapse remain incompletely described. Importantly, growing data from both animal models and humans indicate that exercise can rejuvenate the neuromuscular junction and improve motor function. In this review we will focus on the role of muscle-derived neurotrophin signaling in the rejuvenation of the aged neuromuscular junction in response to exercise.

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Astrocytes, emerging stars of energy homeostasis

Simonetta Camandola1

INTRODUCTION The brain is the organ responsible for the centralized control of the other organs’ functions and, in higher vertebrates, of reasoning. Such tasks are achieved thanks to the interconnections

Base editors: a powerful tool for generating animal models of human diseases

Zongyang Lu1,2 and Xingxu Huang1,3

BASE EDITORS: A NOVEL GENOME ENGINEERING TOOL Genetically engineered mouse models of human diseases have long been used in understanding the underlying mechanisms of the clinically relevant genetic disorders. In

Unweaving the role of nuclear Lamins in neural circuit integrity

Samantha L. Deal1 and Shinya Yamamoto1,2,3,4

Structural integrity of the nuclear membrane is essential for the homeostasis of eukaryotic cells. Critical components of this process are Lamins or type-V intermediate filament proteins that form a meshwork

Alzheimer’s disease: amyloid-based pathogenesis and potential therapies

Yixiu Zhou1, Yuhui Sun2, Quan-Hong Ma2 and Yaobo Liu2

INTRODUCTION Alzheimer’s disease (AD) is one of the most prevalent forms of dementia; in 2015, for example, AD affected ~46.8 million people worldwide. It is estimated that this number will

Membrane closure in stress induced-autophagosome formation

Eiji Morita1

Autophagy (macroautophagy) is a bulk degradation system that sequesters cytoplasmic components by generating double-layered isolation membranes and delivering these isolated contents to the lysosomes [cite]10.1146/annurev-cellbio-092910-154005[/cite]. Though this pathway was originally

Centriolar satellites prevent uncontrolled degradation of centrosome proteins: a speculative review

Nicolas Lecland1 and Andreas Merdes1

INTRODUCTION Centrosomes are cytoplasmic structures that serve as primary microtubule organizing centers in a large variety of animal cells. They consist of a pair of cylindrically shaped centrioles, surrounded by

Novel role of the SIRT4-OPA1 axis in mitochondrial quality control

Alexander Lang1 and Roland P. Piekorz1

Aging is defined by various molecular and cellular hallmarks, among them stem cell exhaustion, genomic instability, altered proteostasis, cellular senescence, and mitochondrial dysfunction [cite]10.1016/j.cell.2013.05.039[/cite]. Mitochondrial defects are considered major drivers