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.
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
Targeting LRH-1/NR5A2 to treat type 1 diabetes mellitus
Nadia Cobo-Vuilleumier1, Petra I. Lorenzo1 and Benoit R. Gauthier1
The liver receptor homolog-1 (LRH-1) is a member of the NR5A family of nuclear receptors that plays a pivotal role in early embryonic development while later on it specifies the
Nucleolar Stress: hallmarks, sensing mechanism and diseases
Kai Yang1,2, Jie Yang1 and Jing Yi1
The nucleolus is a prominent subnuclear compartment, where ribosome biosynthesis takes place. Recently, the nucleolus has gained attention for its novel role in the regulation of cellular stress. Nucleolar stress is emerging as a new concept, which is characterized by diverse cellular insult-induced abnormalities in nucleolar structure and function, ultimately leading to activation of p53 or other stress signaling pathways and alterations in cell behavior. Despite a number of comprehensive reviews on this concept, straightforward and clear-cut way criteria for a nucleolar stress state, regarding the factors that elicit this state, the morphological and functional alterations as well as the rationale for p53 activation are still missing. Based on literature of the past two decades, we herein summarize the evolution of the concept and provide hallmarks of nucleolar stress. Along with updated information and thorough discussion of existing confusions in the field, we pay particular attention to the current understanding of the sensing mechanisms (...)
Calling RNF168 to action
Somaira Nowsheen1 and Zhenkun Lou2
– [table id=103 /] – It is interesting to note that MDC1 acts as a node for the recruitment of both RNF8 and L3MBTL2 and brings these two factors into
Exosomal secretion of truncated cytosolic lysyl-tRNA synthetase induces inflammation during cell starvation
Sang Bum Kim1,2, Seongmin Cho1, 2 and Sunghoon Kim1,2
Kim et al. (2017) reveals three crucial steps of KRS secretion, including its dissociation from the MSC complex, interaction with syntenin, and secretion via the exosomal pathway (Figure 1). –
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.
Targeting LRH-1/NR5A2 to treat type 1 diabetes mellitus
Nadia Cobo-Vuilleumier1, Petra I. Lorenzo1 and Benoit R. Gauthier1
The liver receptor homolog-1 (LRH-1) is a member of the NR5A family of nuclear receptors that plays a pivotal role in early embryonic development while later on it specifies the
Nucleolar Stress: hallmarks, sensing mechanism and diseases
Kai Yang1,2, Jie Yang1 and Jing Yi1
The nucleolus is a prominent subnuclear compartment, where ribosome biosynthesis takes place. Recently, the nucleolus has gained attention for its novel role in the regulation of cellular stress. Nucleolar stress is emerging as a new concept, which is characterized by diverse cellular insult-induced abnormalities in nucleolar structure and function, ultimately leading to activation of p53 or other stress signaling pathways and alterations in cell behavior. Despite a number of comprehensive reviews on this concept, straightforward and clear-cut way criteria for a nucleolar stress state, regarding the factors that elicit this state, the morphological and functional alterations as well as the rationale for p53 activation are still missing. Based on literature of the past two decades, we herein summarize the evolution of the concept and provide hallmarks of nucleolar stress. Along with updated information and thorough discussion of existing confusions in the field, we pay particular attention to the current understanding of the sensing mechanisms (...)
Calling RNF168 to action
Somaira Nowsheen1 and Zhenkun Lou2
– [table id=103 /] – It is interesting to note that MDC1 acts as a node for the recruitment of both RNF8 and L3MBTL2 and brings these two factors into
Exosomal secretion of truncated cytosolic lysyl-tRNA synthetase induces inflammation during cell starvation
Sang Bum Kim1,2, Seongmin Cho1, 2 and Sunghoon Kim1,2
Kim et al. (2017) reveals three crucial steps of KRS secretion, including its dissociation from the MSC complex, interaction with syntenin, and secretion via the exosomal pathway (Figure 1). –
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.
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