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International Review of Cell and Molecular Biology

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https://www.readbyqxmd.com/read/29776606/advances-in-membrane-trafficking-and-endosomal-signaling-of-g-protein-coupled-receptors
#1
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
https://www.readbyqxmd.com/read/29776605/g-protein-coupled-receptor-resensitization-paradigms
#2
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
https://www.readbyqxmd.com/read/29776604/biased-agonism-antagonism-of-cardiovascular-gpcrs-for-heart-failure-therapy
#3
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
https://www.readbyqxmd.com/read/29776603/regulation-of-g-protein-%C3%AE-%C3%AE-signaling
#4
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
https://www.readbyqxmd.com/read/29776602/blurring-boundaries-receptor-tyrosine-kinases-as-functional-g-protein-coupled-receptors
#5
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
https://www.readbyqxmd.com/read/29699693/erk-activation-pathways-downstream-of-gpcrs
#6
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
https://www.readbyqxmd.com/read/29699692/melatonin-receptor-signaling-impact-of-receptor-oligomerization-on-receptor-function
#7
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
https://www.readbyqxmd.com/read/29699691/the-dynamics-of-gpcr-oligomerization-and-their-functional-consequences
#8
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
https://www.readbyqxmd.com/read/29699690/spatiotemporal-modulation-of-erk-activation-by-gpcrs
#9
Uchenna Watson, Ruchi Jain, Suramya Asthana, Deepak K Saini
ERK1/2 (extracellular signal-regulated protein kinases) are the nodal proteins that regulate diverse cellular functions primarily in response to activation from receptor tyrosine kinases (RTKs). Not only is ERK activated through a variety of RTKs, but noncanonical signaling through GPCRs also activates them. Such multimodal activation allows appropriate integration of many inputs to critical cell fate decisions such as proliferation and differentiation that MAP kinases typically regulate. MAP kinases also regulate many polar responses such as apoptosis and proliferation, dedifferentiation-differentiation, and the diversity in the outcomes though the same terminal molecule can be explained based on differences in the activation dynamics and rates...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29699689/follicle-stimulating-hormone-receptor-advances-and-remaining-challenges
#10
Francesco De Pascali, Aurélie Tréfier, Flavie Landomiel, Véronique Bozon, Gilles Bruneau, Romain Yvinec, Anne Poupon, Pascale Crépieux, Eric Reiter
Follicle-stimulating hormone (FSH) is produced in the pituitary and is essential for reproduction. It specifically binds to a membrane receptor (FSHR) expressed in somatic cells of the gonads. The FSH/FSHR system presents many peculiarities compared to classical G protein-coupled receptors (GPCRs). FSH is a large naturally heterogeneous heterodimeric glycoprotein. The FSHR is characterized by a very large NH2-terminal extracellular domain, which binds FSH and participates to the activation/inactivation switch of the receptor...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29551163/lipid-droplets-as-organelles
#11
Sarah Cohen
Long considered inert fat storage depots, it has become clear that lipid droplets (LDs) are bona fide organelles. Like other organelles, they have a characteristic complement of proteins and lipids, and undergo a life cycle that includes biogenesis, maturation, interactions with other organelles, and turnover. I will discuss recent insights into mechanisms governing the life cycle of LDs, and compare and contrast the LD life cycle with that of other metabolic organelles such as mitochondria, peroxisomes, and autophagosomes, highlighting open questions in the field...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29551162/organoids-for-modeling-genetic-diseases
#12
Maria Perez-Lanzon, Guido Kroemer, Maria Chiara Maiuri
In less than a decade, organoid systems have emerged as an innovative and valid in vitro method to mimic in vivo pathophysiology. Organoids are 3D structures constituted by multiple organ-specific cell types that self-organize and can function as miniature organs. Organoids have quickly become an important tool for basic and translational research with wide applications for disease modeling, drug screening, drug optimization, and personalized and regenerative medicine. In this review, we summarize the recent utilization of organoids for modeling human genetic diseases, a research area with promising biomedical applications...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29551161/intracellular-pressure-a-driver-of-cell-morphology-and-movement
#13
Pragati Chengappa, Kimheak Sao, Tia M Jones, Ryan J Petrie
Intracellular pressure, generated by actomyosin contractility and the directional flow of water across the plasma membrane, can rapidly reprogram cell shape and behavior. Recent work demonstrates that cells can generate intracellular pressure with a range spanning at least two orders of magnitude; significantly, pressure is implicated as an important regulator of cell dynamics, such as cell division and migration. Changes to intracellular pressure can dictate the mechanisms by which single human cells move through three-dimensional environments...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29551160/crosstalk-of-autophagy-and-the-secretory-pathway-and-its-role-in-diseases
#14
Muhammad Zahoor, Hesso Farhan
The secretory and autophagic pathways are two fundamental, evolutionary highly conserved endomembrane processes. Typically, secretion is associated with biosynthesis and delivery of proteins. In contrast, autophagy is usually considered as a degradative pathway. Thus, an analogy to metabolic pathways is evident. Anabolic (biosynthetic) and catabolic (degradative) pathways are usually intimately linked and intertwined, and likewise, the secretory and autophagy pathways are intertwined. Investigation of this link is an emerging area of research, and we will provide an overview of some of the major advances that have been made to contribute to understanding of how secretion regulates autophagy and vice versa...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29551159/apoptosis-and-cancer-force-awakens-phantom-menace-or-both
#15
Kai Cao, Stephen W G Tait
Apoptotic cell death serves as an important tumor suppressor mechanism at multiple steps during cancer progression. Equally, engagement of apoptosis represents a potent therapeutic effector mechanism. Nevertheless, the role of apoptosis in cancer may be more complex than previously thought. Indeed, various studies have found that apoptosis signaling also has oncogenic potential. In this review, we discuss how apoptosis can promote cancer and how these effects might be targeted to optimize apoptosis-inducing anticancer therapy...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29551158/the-lymphatic-fluid
#16
Laura Santambrogio
This review will highlight our current understanding of the formation, circulation, and immunological role of lymphatic fluid. The formation of the extracellular fluid depends on the net balance between the hydrostatic and osmotic pressure gradients effective in the capillary beds. Lymph originates from the extracellular fluid and its composition combines the ultrafiltrated plasma proteins with the proteome generated by the metabolic activities of each parenchymal tissue. Several analyses have indicated how the lymph composition reflects the organs' physiological and pathological states...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29551157/karyosphere-karyosome-a-peculiar-structure-of-the-oocyte-nucleus
#17
Dmitry S Bogolyubov
The karyosphere, aka the karyosome, is a meiosis-specific structure that represents a "knot" of condensed chromosomes joined together in a limited volume of the oocyte nucleus. The karyosphere is an evolutionarily conserved but morphologically rather "multifaceted" structure. It forms at the diplotene stage of meiotic prophase in many animals, from hydra and Drosophila to human. Karyosphere formation is generally linked with transcriptional silencing of the genome. It is believed that karyosphere/karyosome is a prerequisite for proper completion of meiotic divisions and further development...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29413894/altered-metabolism-of-leukemic-cells-new-therapeutic-opportunity
#18
Julia Starkova, Ivana Hermanova, Katerina Hlozkova, Alzbeta Hararova, Jan Trka
The cancer metabolic program alters bioenergetic processes to meet the higher demands of tumor cells for biomass production, nucleotide synthesis, and NADPH-balancing redox homeostasis. It is widely accepted that cancer cells mostly utilize glycolysis, as opposed to normal cells, in which oxidative phosphorylation is the most employed bioenergetic process. Still, studies examining cancer metabolism had been overlooked for many decades, and it was only recently discovered that metabolic alterations affect both the oncogenic potential and therapeutic response...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29413893/new-insights-into-autophagy-dysfunction-related-to-amyloid-beta-toxicity-and-neuropathology-in-alzheimer-s-disease
#19
Claudia Ntsapi, Dumisile Lumkwana, Chrisna Swart, Andre du Toit, Ben Loos
The fine control of neuronal proteostasis is an essential element that preserves cell viability. Advancing age is a major risk factor for Alzheimer's disease (AD), and autophagy is thought to dictate normal and pathological aging through intricate molecular machinery controlling protein aggregation. Although the role of autophagy dysfunction in AD is known, the dynamic changes during the progression of the disease remain unclear. Recent studies have provided new insight into the molecular mechanisms that link defective autophagy and cellular fate, underscoring the pathogenic events associated with AD...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29413892/mechanisms-of-cortical-differentiation
#20
Lata Adnani, Sisu Han, Saiqun Li, Pierre Mattar, Carol Schuurmans
During fetal and postnatal development, the human brain generates 160 billion neuronal and glial cells, each with precise cellular phenotypes. To effectively manage such a complicated task, intrinsic (e.g., transcription factors) and extrinsic (environmental signals) cues cooperate to regulate the decision by neural progenitors to continue to proliferate or to differentiate. Loss- and gain-of-function studies in the mouse brain have been instrumental in identifying these cues, leading to a fairly well-developed and well-integrated model of neocortical development...
2018: International Review of Cell and Molecular Biology
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