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.
Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells
Lyssia Belarif1, Bernard Vanhove1 and Nicolas Poirier1
Targeting proinflammatory cytokines such as TNFα, IL-1, IL-6, is clinically beneficial in several immune-mediated inflammatory diseases (IMID). However, these cytokines are downstream mediators of immune responses that show poor impact
TRIM16 employs NRF2, ubiquitin system and aggrephagy for safe disposal of stress-induced misfolded proteins
Kautilya Kumar Jena1,2, Subhash Mehto1, Srinivasa Prasad Kolapalli1, Parej Nath1, Swati Chauhan1 and Santosh Chauhan1
We found that under oxidative or proteotoxic stress conditions, the TRIM16 is required for biogenesis of protein aggregates from misfolded proteins. In our attempt to investigate the mechanism by which
Systemic signalling and local effectors in developmental stability, body symmetry, and size
Sergio Juarez-Carreño1, Javier Morante1 and Maria Dominguez1
Symmetric growth and the origins of fluctuating asymmetry are unresolved phenomena of biology. Small, and sometimes noticeable, deviations from perfect bilateral symmetry reflect the vulnerability of development to perturbations. The degree of asymmetry is related to the magnitude of the perturbations and the ability of an individual to cope with them. As the left and right sides of an individual were presumed to be genetically identical, deviations of symmetry were traditionally attributed to non-genetic effects such as environmental and developmental noise. In this review, we draw attention to other possible sources of variability, especially to somatic mutations and transposons. Mutations are a major source of phenotypic variability and recent genomic data have highlighted somatic mutations as ubiquitous, even in phenotypically normal individuals. We discuss the importance of factors that are responsible for buffering and stabilizing the genome (...)
Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase
Harald Steiner1,2, Akio Fukumori3, Shinji Tagami4 and Masayasu Okochi4
Alzheimer´s disease (AD) is a devastating neurodegenerative disease of the elderly population. Genetic evidence strongly suggests that aberrant generation and/or clearance of the neurotoxic amyloid-β peptide (Aβ) is triggering the disease. Aβ is generated from the amyloid precursor protein (APP) by the sequential cleavages of β- and γ-secretase. The latter cleavage by γ-secretase, a unique and fascinating four-component protease complex, occurs in the APP transmembrane domain thereby releasing Aβ species of 37-43 amino acids in length including the longer, highly pathogenic peptides Aβ42 and Aβ43. The lack of a precise understanding of Aβ generation as well as of the functions of other γ-secretase substrates has been one factor underlying the disappointing failure of γ-secretase inhibitors in clinical trials, but on the other side also been a major driving force for structural and in depth mechanistic studies on this key AD drug target in the past few years. Here we (...)
Mechanisms and therapeutic significance of autophagy modulation by antipsychotic drugs
Ljubica Vucicevic1, Maja Misirkic-Marjanovic1, Ljubica Harhaji-Trajkovic1, Nadja Maric2 and Vladimir Trajkovic3
INTRODUCTION The term autophagy (‘self-eating’ in Greek) refers to a group of evolutionarily conserved homeostatic mechanisms employed by eukaryotic cells to eliminate aged, unused, and damaged cytoplasmic components through lysosomal
p53 and energy balance: meeting hypothalamic AgRP neurons
Omar Al-Massadi1,2,#, Mar Quiñones1,2,#, Ruben Nogueiras1,2
Cancer cells undergo profound metabolic changes to cope with the high energy demand for cell growth and division. Given the importance of this metabolic reprogramming in tumor development, it seems
Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells
Lyssia Belarif1, Bernard Vanhove1 and Nicolas Poirier1
Targeting proinflammatory cytokines such as TNFα, IL-1, IL-6, is clinically beneficial in several immune-mediated inflammatory diseases (IMID). However, these cytokines are downstream mediators of immune responses that show poor impact
TRIM16 employs NRF2, ubiquitin system and aggrephagy for safe disposal of stress-induced misfolded proteins
Kautilya Kumar Jena1,2, Subhash Mehto1, Srinivasa Prasad Kolapalli1, Parej Nath1, Swati Chauhan1 and Santosh Chauhan1
We found that under oxidative or proteotoxic stress conditions, the TRIM16 is required for biogenesis of protein aggregates from misfolded proteins. In our attempt to investigate the mechanism by which
Systemic signalling and local effectors in developmental stability, body symmetry, and size
Sergio Juarez-Carreño1, Javier Morante1 and Maria Dominguez1
Symmetric growth and the origins of fluctuating asymmetry are unresolved phenomena of biology. Small, and sometimes noticeable, deviations from perfect bilateral symmetry reflect the vulnerability of development to perturbations. The degree of asymmetry is related to the magnitude of the perturbations and the ability of an individual to cope with them. As the left and right sides of an individual were presumed to be genetically identical, deviations of symmetry were traditionally attributed to non-genetic effects such as environmental and developmental noise. In this review, we draw attention to other possible sources of variability, especially to somatic mutations and transposons. Mutations are a major source of phenotypic variability and recent genomic data have highlighted somatic mutations as ubiquitous, even in phenotypically normal individuals. We discuss the importance of factors that are responsible for buffering and stabilizing the genome (...)
Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase
Harald Steiner1,2, Akio Fukumori3, Shinji Tagami4 and Masayasu Okochi4
Alzheimer´s disease (AD) is a devastating neurodegenerative disease of the elderly population. Genetic evidence strongly suggests that aberrant generation and/or clearance of the neurotoxic amyloid-β peptide (Aβ) is triggering the disease. Aβ is generated from the amyloid precursor protein (APP) by the sequential cleavages of β- and γ-secretase. The latter cleavage by γ-secretase, a unique and fascinating four-component protease complex, occurs in the APP transmembrane domain thereby releasing Aβ species of 37-43 amino acids in length including the longer, highly pathogenic peptides Aβ42 and Aβ43. The lack of a precise understanding of Aβ generation as well as of the functions of other γ-secretase substrates has been one factor underlying the disappointing failure of γ-secretase inhibitors in clinical trials, but on the other side also been a major driving force for structural and in depth mechanistic studies on this key AD drug target in the past few years. Here we (...)
Mechanisms and therapeutic significance of autophagy modulation by antipsychotic drugs
Ljubica Vucicevic1, Maja Misirkic-Marjanovic1, Ljubica Harhaji-Trajkovic1, Nadja Maric2 and Vladimir Trajkovic3
INTRODUCTION The term autophagy (‘self-eating’ in Greek) refers to a group of evolutionarily conserved homeostatic mechanisms employed by eukaryotic cells to eliminate aged, unused, and damaged cytoplasmic components through lysosomal
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,
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.
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