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International Review of Cell and Molecular Biology

Jolanda Brummelman, Karolina Pilipow, Enrico Lugli
On antigen encounter, naïve CD8+ and CD4+ T cells differentiate into a large number of effector cells that migrate to inflamed tissues to fight infections or tumors. Following elimination of the target, a few cells remain in the long-term, the so-called memory T cells that are capable to reexpand and respond more vigorously on a second encounter with the cognate antigen. While the naïve T cell compartment is fairly homogenous, effector and memory T cells are largely diverse, comprising dozens of subsets with diverse functions, molecular characteristics, and localization in the body...
2018: International Review of Cell and Molecular Biology
John W Hickey, Alyssa K Kosmides, Jonathan P Schneck
T cells are crucial contributors to mounting an effective immune response and increasingly the focus of therapeutic interventions in cancer, infectious disease, and autoimmunity. Translation of current T cell immunotherapies has been hindered by off-target toxicities, limited efficacy, biological variability, and high costs. As T cell therapeutics continue to develop, the application of engineering concepts to control their delivery and presentation will be critical for their success. Here, we outline the engineer's toolbox and contextualize it with the biology of T cells...
2018: International Review of Cell and Molecular Biology
Adrienne E Borrie, Saman Maleki Vareki
Immunotherapy represents a breakthrough in cancer treatment in the past decade. It is a powerful treatment modality that can help transform cancer into a manageable disease by enabling the immune system to eliminate tumor cells. Advances in the use of immune checkpoint inhibitors, adoptive cell therapy, and oncolytic viruses have led to exceptional and durable clinical responses in patients with late-stage disease. Here we discuss some approved or under investigation immunotherapeutics that either directly involve T-cells such as chimeric antigen receptor T-cells and checkpoint inhibitors or lead to the activation of T-cells such as oncolytic viruses...
2018: International Review of Cell and Molecular Biology
Nicolas Pallet, Ana A Fernández-Ramos, Marie-Anne Loriot
Energetic metabolism supports rapid cell growth and proliferation, differentiation, polarization, and effector functions of T cells. T lymphocytes have the remarkable plasticity that allows them to shape their metabolism to adapt to extracellular and intracellular cues, a process that involves molecular modules referred to as "metabolic checkpoints" that sense metabolic signals and transduce effector messages. These metabolic checkpoints may represent a novel therapeutic strategy for immune modulation...
2018: International Review of Cell and Molecular Biology
Uqba Khan, Hareem Ghazanfar
T lymphocytes play a central role in regulation of the immune system. Both effector and regulatory T cells work in equilibrium to provide optimal immune response against foreign pathogens. Normally, T cells do not react against self-antigens because of the presence of central and peripheral immunogenic tolerance. Central tolerance eliminates autoreactive naive T cells that develop in thymus by presenting them with self-antigens on the thymic cells. The autoreactive T cells that escape thymus are subjected to additional mechanisms such as clonal anergy, ignorance, and deletion...
2018: International Review of Cell and Molecular Biology
Fanny Chalmin, Etienne Humblin, François Ghiringhelli, Frédérique Végran
Understanding the basis of cellular differentiation is a fundamental issue in developmental biology but also for the comprehension of pathological processes. In fact, the palette of developmental decisions for naive CD4 T cells is a critical aspect of the development of appropriate immune responses which could control infectious processes or cancer growth. However, the current accumulation of data on CD4 T cells biology reveals a complex world with different helper populations. Naive CD4 T cells can differentiate into different subtypes in response to cytokine stimulation...
2018: International Review of Cell and Molecular Biology
Justine Lebeau, T Kelly Rainbolt, R Luke Wiseman
Proteases are localized throughout mitochondria and function as critical regulators of all aspects of mitochondrial biology. As such, the activities of these proteases are sensitively regulated through transcriptional and post-translational mechanisms to adapt mitochondrial function to specific cellular demands. Here, we discuss the stress-responsive mechanisms responsible for regulating mitochondrial protease activity and the implications of this regulation on mitochondrial function. Furthermore, we describe how imbalances in the activity or regulation of mitochondrial proteases induced by genetic, environmental, or aging-related factors influence mitochondria in the context of disease...
2018: International Review of Cell and Molecular Biology
Clea Bárcena, Pablo Mayoral, Pedro M Quirós
Mitohormesis is a term used to define a biological response where the induction of a reduced amount of mitochondrial stress leads to an increment in health and viability within a cell, tissue, or organism. The mitochondrial stress response activated by a potentially damaging stimulus requires a coordinated dialogue with the cellular nucleus, known as mitonuclear communication. This interplay induced by the hormetic response in mitochondria relies in a variety of signals among which the most relevant ones are reactive oxygen species (ROS), mitochondrial metabolites, proteotoxic signals, the mitochondria-cytosol stress response, and the release of mitokines...
2018: International Review of Cell and Molecular Biology
Carlotta Giorgi, Saverio Marchi, Ines C M Simoes, Ziyu Ren, Giampaolo Morciano, Mariasole Perrone, Paulina Patalas-Krawczyk, Sabine Borchard, Paulina Jędrak, Karolina Pierzynowska, Jędrzej Szymański, David Q Wang, Piero Portincasa, Grzegorz Węgrzyn, Hans Zischka, Pawel Dobrzyn, Massimo Bonora, Jerzy Duszynski, Alessandro Rimessi, Agnieszka Karkucinska-Wieckowska, Agnieszka Dobrzyn, Gyorgy Szabadkai, Barbara Zavan, Paulo J Oliveira, Vilma A Sardao, Paolo Pinton, Mariusz R Wieckowski
Aging has been linked to several degenerative processes that, through the accumulation of molecular and cellular damage, can progressively lead to cell dysfunction and organ failure. Human aging is linked with a higher risk for individuals to develop cancer, neurodegenerative, cardiovascular, and metabolic disorders. The understanding of the molecular basis of aging and associated diseases has been one major challenge of scientific research over the last decades. Mitochondria, the center of oxidative metabolism and principal site of reactive oxygen species (ROS) production, are crucial both in health and in pathogenesis of many diseases...
2018: International Review of Cell and Molecular Biology
Maria Markaki, Konstantinos Palikaras, Nektarios Tavernarakis
Aging is a complex biological process affecting almost all living organisms. Although its detrimental effects on animals' physiology have been extensively documented, several aspects of the biology of aging are insufficiently understood. Mitochondria, the central energy producers of the cell, play vital roles in a wide range of cellular processes, including regulation of bioenergetics, calcium signaling, metabolic responses, and cell death, among others. Thus, proper mitochondrial function is a prerequisite for the maintenance of cellular and organismal homeostasis...
2018: International Review of Cell and Molecular Biology
Carles Cantó
Despite their classic bean-shaped depiction, mitochondria have very different aspects in each cell type. From long filamentous structures to punctuated small round organelles. These shapes can dynamically change in response to nutrients and in situations of metabolic disease. However, why do mitochondria adapt different shapes and how is this determined? In this review, we will aim to understand different visions on how metabolic cues influence mitochondrial shape and vice-versa. This response can be dramatically different between tissues and cells, as illustrated by a large array of genetically engineered mouse models reported to date...
2018: International Review of Cell and Molecular Biology
Giacomo Baccolo, Giulia Stamerra, Coppola Damiano Pellegrino, Ivan Orlandi, Marina Vai
Mitochondrial functionality is one of the main factors involved in cell survival, and mitochondrial dysfunctions have been identified as an aging hallmark. In particular, the insurgence of mitochondrial dysfunctions is tightly connected to mitochondrial metabolism. During aging, both mitochondrial oxidative and biosynthetic metabolisms are progressively altered, with the development of malfunctions, in turn affecting mitochondrial functionality. In this context, the relation between mitochondrial pathways and aging is evolutionarily conserved from single-celled organisms, such as yeasts, to complex multicellular organisms, such as humans...
2018: International Review of Cell and Molecular Biology
Aylin C Hanyaloglu
The integration of GPCR signaling with membrane trafficking, as a single orchestrated system, is a theme increasingly evident with the growing reports of GPCR endosomal signaling. Once viewed as a mechanism to regulate cell surface heterotrimeric G protein signaling, the endocytic trafficking system is complex, highly compartmentalized, yet deeply interconnected with cell signaling. The organization of receptors into distinct plasma membrane signalosomes, biochemically distinct endosomal populations, endosomal microdomains, and its communication with distinct subcellular organelles such as the Golgi provides multiple unique signaling platforms that are critical for specifying receptor function physiologically and pathophysiologically...
2018: International Review of Cell and Molecular Biology
Manveen K Gupta, Maradumane L Mohan, Sathyamangla V Naga Prasad
Cellular responses to extracellular milieu/environment are driven by cell surface receptors that transmit the signal into the cells resulting in a synchronized and measured response. The ability to provide such exquisite responses to changes in external environment is mediated by the tight and yet, deliberate regulation of cell surface receptor function. In this regard, the seven transmembrane G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors that regulate responses like cardiac contractility, vision, and olfaction including platelet activation...
2018: International Review of Cell and Molecular Biology
Victoria L Desimine, Katie A McCrink, Barbara M Parker, Shelby L Wertz, Jennifer Maning, Anastasios Lymperopoulos
G protein-coupled receptors (GPCRs) are among the most important drug targets currently used in clinic, including drugs for cardiovascular indications. We now know that, in addition to activating heterotrimeric G protein-dependent signaling pathways, GPCRs can also activate G protein-independent signaling, mainly via the βarrestins. The major role of βarrestin1 and -2, also known as arrestin2 or -3, respectively, is to desensitize GPCRs, i.e., uncoupled them from G proteins, and to subsequently internalize the receptor...
2018: International Review of Cell and Molecular Biology
Kanishka Senarath, Dinesh Kankanamge, Saroopa Samaradivakara, Kasun Ratnayake, Mithila Tennakoon, Ajith Karunarathne
Heterotrimeric guanine nucleotide-binding proteins (G proteins) deliver external signals to the cell interior, upon activation by the external signal stimulated G protein-coupled receptors (GPCRs).While the activated GPCRs control several pathways independently, activated G proteins control the vast majority of cellular and physiological functions, ranging from vision to cardiovascular homeostasis. Activated GPCRs dissociate GαGDPβγ heterotrimer into GαGTP and free Gβγ. Earlier, GαGTP was recognized as the primary signal transducer of the pathway and Gβγ as a passive signaling modality that facilitates the activity of Gα...
2018: International Review of Cell and Molecular Biology
Caitrin Crudden, Takashi Shibano, Dawei Song, Naida Suleymanova, Ada Girnita, Leonard Girnita
Receptor tyrosine kinases (RTKs) such as the insulin-like growth factor type 1 receptor (IGF-1R) control important biological activities as well as being involved in pathological processes. Due to their supportive nature in many human cancers they have long been considered attractive therapeutic targets. However, lessons learnt from early targeting trials highlight that a simple "active versus inactive" state model with classical kinase-only signaling is overly simplistic and does not describe reality...
2018: International Review of Cell and Molecular Biology
Ruchi Jain, Uchenna Watson, Lakshmi Vasudevan, Deepak K Saini
GPCRs, the 7-TM receptors, represent a class of cell surface receptors which modulate a variety of physiological responses. The serpentine structure in addition to contributing the diversity of stimuli these receptors can sense also provides flexibility to the extracellular and intracellular regions where other proteins can interact with and can form functionally active multimeric entities. The range in signaling and physiological responses generated by these receptors can be attributed to a large repertoire of the receptor subtypes as well as their differential coupling to various classes of G-protein subunits and other proteins which facilitate multistate activation...
2018: International Review of Cell and Molecular Biology
Atsuro Oishi, Erika Cecon, Ralf Jockers
The melatonin receptor subfamily is composed of three members, MT1 and MT2 , which are binding to melatonin, and GPR50, which shows high sequence homology to MT1 and MT2 but does not bind to melatonin or any other known ligand. An interesting feature of these receptors is their capacity to form homo- and heteromers between each other and also with other GPCRs. The following heteromers have been described: MT1 /MT2 , MT1 /GPR50, and heteromers composed of MT2 and the serotonin 5-HT2c receptor or the orphan GPR61, GPR62, and GPR135 receptors...
2018: International Review of Cell and Molecular Biology
Rory Sleno, Terence E Hébert
The functional importance of G protein-coupled receptor (GPCR) oligomerization remains controversial. Although obligate dimers of class C GPCRs are well accepted, the generalizability of this phenomenon is still strongly debated with respect to other classes of GPCRs. In this review, we focus on understanding the organization and dynamics between receptor equivalents and their signaling partners in oligomeric receptor complexes, with a view toward integrating disparate viewpoints into a unified understanding...
2018: International Review of Cell and Molecular Biology
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