scholarly journals The emerging role of phosphoinositide clustering in intracellular trafficking and signal transduction

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 422 ◽  
Author(s):  
Laura Picas ◽  
Frederique Gaits-Iacovoni ◽  
Bruno Goud
Keyword(s):  
Signal Transduction ◽  
Intracellular Trafficking ◽  
Recent Observation ◽  
Metabolizing Enzymes ◽  
Master Regulators ◽  
Cellular Processes ◽  
Cellular Compartments ◽  
Cytoskeleton Dynamics ◽  
Protein Modules

Phosphoinositides are master regulators of multiple cellular processes: from vesicular trafficking to signaling, cytoskeleton dynamics, and cell growth. They are synthesized by the spatiotemporal regulated activity of phosphoinositide-metabolizing enzymes. The recent observation that some protein modules are able to cluster phosphoinositides suggests that alternative or complementary mechanisms might operate to stabilize the different phosphoinositide pools within cellular compartments. Herein, we discuss the different known and potential molecular players that are prone to engage phosphoinositide clustering and elaborate on how such a mechanism might take part in the regulation of intracellular trafficking and signal transduction.

Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease

2011 ◽  
Vol 439 (3) ◽  
pp. 349-378 ◽  
Author(s):  
Anthony J. Morgan ◽  
Frances M. Platt ◽  
Emyr Lloyd-Evans ◽  
Antony Galione
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Processes ◽  
Late Endosomes ◽  
Wide Range ◽  
Health And Disease ◽  
Lysosome Related Organelles ◽  
Cellular Compartments ◽  
Endosomal Vesicles ◽  
Intracellular Targets

Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In particular, we discuss the role of the Ca2+-mobilizing messenger NAADP (nicotinic acid adenine dinucleotide phosphate) as a major regulator of Ca2+ release from endolysosomes, and the recent discovery of an endolysosomal channel family, the TPCs (two-pore channels), as its principal intracellular targets. Recent molecular studies of endolysosomal Ca2+ physiology and its regulation by NAADP-gated TPCs are providing exciting new insights into the mechanisms of Ca2+-signal initiation that control a wide range of cellular processes and play a role in disease. These developments underscore a new central role for the endolysosomal system in cellular Ca2+ regulation and signalling.

Regulation of hemidesmosome dynamics and cell signaling by integrin α6β4

2021 ◽  
Vol 134 (18) ◽  
Author(s):  
Lisa te Molder ◽  
Jose M. de Pereda ◽  
Arnoud Sonnenberg
Keyword(s):  
Signal Transduction ◽  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Cellular Processes ◽  
Integrin Α6β4

ABSTRACT Hemidesmosomes (HDs) are specialized multiprotein complexes that connect the keratin cytoskeleton of epithelial cells to the extracellular matrix (ECM). In the skin, these complexes provide stable adhesion of basal keratinocytes to the underlying basement membrane. Integrin α6β4 is a receptor for laminins and plays a vital role in mediating cell adhesion by initiating the assembly of HDs. In addition, α6β4 has been implicated in signal transduction events that regulate diverse cellular processes, including proliferation and survival. In this Review, we detail the role of α6β4 in HD assembly and beyond, and we discuss the molecular mechanisms that regulate its function.

The role of Rsp5 ubiquitin ligase in regulation of diverse processes in yeast cells.

2008 ◽  
Vol 55 (4) ◽  
pp. 649-662 ◽  
Author(s):  
Paweł Kaliszewski ◽  
Teresa Zoładek
Keyword(s):  
Fatty Acid ◽  
Ubiquitin Ligase ◽  
Intracellular Trafficking ◽  
Phospholipid Composition ◽  
Multivesicular Body ◽  
Yeast Cells ◽  
Sterol Synthesis ◽  
Cellular Processes ◽  
Number Of Publications

Rsp5 is a conserved ubiquitin ligase involved in regulation of numerous cellular processes. A growing number of publications describing new functions of the ligase have appeared in recent years. Rsp5 was shown to be involved in the control of intracellular trafficking of proteins via endocytosis and multivesicular body sorting. Moreover, nuclear functions of Rsp5 in response to various stresses have been discovered. Rsp5 is also involved in the regulation of unsaturated fatty acid and sterol synthesis and phospholipid composition. Here, an overview of Rsp5 functions with emphasis on its involvement in the regulation of lipid biosynthesis will be presented.

scholarly journals Role of Cytosolic 2-Cys Prx1 and Prx2 in Redox Signaling

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 169 ◽  
Author(s):  
Yosup Kim ◽  
Ho Hee Jang
Keyword(s):  
Redox Status ◽  
Redox Signaling ◽  
Amino Acid Sequences ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Interaction Partners ◽  
Catalytic Cysteine ◽  
Cellular Compartments ◽  
Dependent Mechanism

Peroxiredoxins (Prxs), a family of peroxidases, are reactive oxygen species scavengers that hydrolyze H2O2 through catalytic cysteine. Mammalian Prxs comprise six isoforms (typical 2-Cys Prxs; Prx1–4, atypical 2-Cys Prx; Prx5, and 1-Cys Prx; Prx6) that are distributed over various cellular compartments as they are classified according to the position and number of conserved cysteine. 2-Cys Prx1 and Prx2 are abundant proteins that are ubiquitously expressed mainly in the cytosol, and over 90% of their amino acid sequences are homologous. Prx1 and Prx2 protect cells from ROS-mediated oxidative stress through the elimination of H2O2 and regulate cellular signaling through redox-dependent mechanism. In addition, Prx1 and Prx2 are able to bind to a diversity of interaction partners to regulate other various cellular processes in cancer (i.e., regulation of the protein redox status, cell growth, apoptosis, and tumorigenesis). Thus, Prx1 and Prx2 can be potential therapeutic targets and it is particularly important to control their level or activity. This review focuses on cytosolic 2-Cys Prx1 and Prx2 and their role in the regulation of redox signaling based on protein-protein interaction.

NH2 terminus of serum and glucocorticoid-regulated kinase 1 binds to phosphoinositides and is essential for isoform-specific physiological functions

2007 ◽  
Vol 292 (6) ◽  
pp. F1741-F1750 ◽  
Author(s):  
Alan C. Pao ◽  
James A. McCormick ◽  
Hongyan Li ◽  
John Siu ◽  
Cedric Govaerts ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kinase Activity ◽  
Regulatory Protein ◽  
Forkhead Transcription Factor ◽  
Cellular Processes ◽  
Cellular Compartments ◽  
Stimulation Of

Serum and glucocorticoid regulated kinase 1 (SGK1) has been identified as a key regulatory protein that controls a diverse set of cellular processes including sodium (Na+) homeostasis, osmoregulation, cell survival, and cell proliferation. Two other SGK isoforms, SGK2 and SGK3, have been identified, which differ most markedly from SGK1 in their NH2-terminal domains. We found that SGK1 and SGK3 are potent stimulators of epithelial Na+ channel (ENaC)-dependent Na+ transport, while SGK2, which has a short NH2 terminus, is a weak stimulator of ENaC. Further characterization of the role of the SGK1 NH2 terminus revealed that its deletion does not affect in vitro kinase activity but profoundly limits the ability of SGK1 either to stimulate ENaC-dependent Na+ transport or inhibit Forkhead-dependent gene transcription. The NH2 terminus of SGK1, which shares sequence homology with the phosphoinositide 3-phosphate [PI( 3 )P] binding domain of SGK3, binds phosphoinositides in protein lipid overlay assays, interacting specifically with PI( 3 )P, PI( 4 )P, and PI( 5 )P, but not with PI( 3 , 4 , 5 )P3. Moreover, a point mutation that reduces phosphoinositide binding to the NH2 terminus also reduces SGK1 effects on Na+ transport and Forkhead activity. These data suggest that the NH2 terminus, although not required for PI 3-kinase-dependent modulation of SGK1 catalytic activity, is required for multiple SGK1 functions, including stimulation of ENaC and inhibition of the proapoptotic Forkhead transcription factor. Together, these observations support the idea that the NH2-terminal domain acts downstream of PI 3-kinase-dependent activation to target the kinase to specific cellular compartments and/or substrates, possibly through its interactions with a subset of phosphoinositides.

scholarly journals A tumor suppressive long noncoding RNA, DRAIC, inhibits protein translation and induces autophagy by activating AMPK

2021 ◽  
Author(s):  
Shekhar Saha ◽  
Ying Zhang ◽  
Briana Wilson ◽  
Roger Abounader ◽  
Anindya Dutta
Keyword(s):  
Signal Transduction ◽  
Noncoding Rna ◽  
Protein Translation ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Castration Resistant ◽  
Iκb Kinase ◽  
Downstream Effects

LncRNAs are long RNA transcripts that do not code for proteins and that have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA which is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-kB pathway by inhibiting the IκB kinase. Decreased DRAIC expression predicted poor patient outcome in gliomas and seven other cancers. We now report that DRAIC suppresses invasion, migration, colony formation and xenograft growth of glioblastoma derived cell lines. DRAIC activates AMPK by downregulating the NF-κB target gene GLUT1, and thus represses mTOR, leading to downstream effects such as decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis: the NF-κB pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-κB, protein translation and autophagy by the same lncRNA explains the tumor suppressive role of DRAIC in different cancers and reinforces the importance of lncRNAs as emerging regulators of signal transduction pathways.

scholarly journals The Sarcomeric M-Region: A Molecular Command Center for Diverse Cellular Processes

2015 ◽  
Vol 2015 ◽  
pp. 1-25 ◽  
Author(s):  
Li-Yen R. Hu ◽  
Maegen A. Ackermann ◽  
Aikaterini Kontrogianni-Konstantopoulos
Keyword(s):  
Signal Transduction ◽  
Thick Filament ◽  
Cellular Processes ◽  
Cytoskeletal Remodeling ◽  
Filament Assembly ◽  
Thick Filaments ◽  
Genes Encoding ◽  
Related Proteins ◽  
Command Center

The sarcomeric M-region anchors thick filaments and withstands the mechanical stress of contractions by deformation, thus enabling distribution of physiological forces along the length of thick filaments. While the role of the M-region in supporting myofibrillar structure and contractility is well established, its role in mediating additional cellular processes has only recently started to emerge. As such, M-region is the hub of key protein players contributing to cytoskeletal remodeling, signal transduction, mechanosensing, metabolism, and proteasomal degradation. Mutations in genes encoding M-region related proteins lead to development of severe and lethal cardiac and skeletal myopathies affecting mankind. Herein, we describe the main cellular processes taking place at the M-region, other than thick filament assembly, and discuss human myopathies associated with mutant or truncated M-region proteins.

scholarly journals Regulation of Glucose Metabolism by NAD+ and ADP-Ribosylation

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 890 ◽  
Author(s):  
Hopp ◽  
Grüter ◽  
Hottiger
Keyword(s):  
Glucose Metabolism ◽  
Metabolic Pathways ◽  
Redox Reactions ◽  
Genotoxic Stress ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Cellular Processes ◽  
Energy Needs ◽  
Cellular Compartments

Cells constantly adapt their metabolic pathways to meet their energy needs and respond to nutrient availability. During the last two decades, it has become increasingly clear that NAD+, a coenzyme in redox reactions, also mediates several ubiquitous cell signaling processes. Protein ADP-ribosylation is a post-translational modification that uses NAD+ as a substrate and is best known as part of the genotoxic stress response. However, there is increasing evidence that NAD+-dependent ADP-ribosylation regulates other cellular processes, including metabolic pathways. In this review, we will describe the compartmentalized regulation of NAD+ biosynthesis, consumption, and regeneration with a particular focus on the role of ADP-ribosylation in the regulation of glucose metabolism in different cellular compartments.

scholarly journals Unbalanced Sphingolipid Metabolism and Its Implications for the Pathogenesis of Psoriasis

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1130 ◽  
Author(s):  
Katarzyna Bocheńska ◽  
Magdalena Gabig-Cimińska
Keyword(s):  
Skin Barrier ◽  
Immune Dysregulation ◽  
Sphingolipid Metabolism ◽  
Complex Interplay ◽  
Signalling Molecules ◽  
Cellular Processes ◽  
Immune Mediated ◽  
Diseased Skin ◽  
Cellular Compartments

Sphingolipids (SLs), which have structural and biological responsibilities in the human epidermis, are importantly involved in the maintenance of the skin barrier and regulate cellular processes, such as the proliferation, differentiation and apoptosis of keratinocytes (KCs). As many dermatologic diseases, including psoriasis (PsO), intricately characterized by perturbations in these cellular processes, are associated with altered composition and unbalanced metabolism of epidermal SLs, more education to precisely determine the role of SLs, especially in the pathogenesis of skin disorders, is needed. PsO is caused by a complex interplay between skin barrier disruption, immune dysregulation, host genetics and environmental triggers. The contribution of particular cellular compartments and organelles in SL metabolism, a process related to dysfunction of lysosomes in PsO, seems to have a significant impact on lysosomal signalling linked to a modulation of the immune-mediated inflammation accompanying this dermatosis and is not fully understood. It is also worth noting that a prominent skin disorder, such as PsO, has diminished levels of the main epidermal SL ceramide (Cer), reflecting altered SL metabolism, that may contribute not only to pathogenesis but also to disease severity and/or progression. This review provides a brief synopsis of the implications of SLs in PsO, aims to elucidate the roles of these molecules in complex cellular processes deregulated in diseased skin tissue and highlights the need for increased research in the field. The significance of SLs as structural and signalling molecules and their actions in inflammation, in which these components are factors responsible for vascular endothelium abnormalities in the development of PsO, are discussed.

scholarly journals A tumor suppressive long noncoding RNA, DRAIC, inhibits protein translation and induces autophagy by activating AMPK

2021 ◽  
Author(s):  
Shekhar Saha ◽  
Ying Zhang ◽  
Briana Wilson ◽  
Roger Abounader ◽  
Anindya Dutta
Keyword(s):  
Signal Transduction ◽  
Noncoding Rna ◽  
Target Gene ◽  
Protein Translation ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Castration Resistant ◽  
Downstream Effects

LncRNAs are long RNA transcripts that do not code for proteins and that have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA which is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-κB pathway by inhibiting the IκBαkinase. Decreased DRAIC expression predicted poor patient outcome in gliomas and seven other cancers. We now report that DRAIC suppresses invasion, migration, colony formation and xenograft growth of glioblastoma derived cell lines. DRAIC activates AMPK by downregulating the NF-κB target gene GLUT1, and thus represses mTOR, leading to downstream effects such as decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis: the NF-κB pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-κB, protein translation and autophagy by the same lncRNA explains the tumor suppressive role of DRAIC in different cancers and reinforces the importance of lncRNAs as emerging regulators of signal transduction pathways.

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