Deubiquitylating enzymes in receptor endocytosis and trafficking

2016 ◽  
Vol 473 (24) ◽  
pp. 4507-4525 ◽  
Author(s):  
Aidan P. McCann ◽  
Christopher J. Scott ◽  
Sandra Van Schaeybroeck ◽  
James F. Burrows
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Therapeutic Targets ◽  
Multivesicular Body ◽  
Lysosomal Degradation ◽  
Transmembrane Receptors ◽  
Receptor Endocytosis ◽  
Cellular Processes

In recent times, our knowledge of the roles ubiquitin plays in multiple cellular processes has expanded exponentially, with one example being the role of ubiquitin in receptor endocytosis and trafficking. This has prompted a multitude of studies examining how the different machinery involved in the addition and removal of ubiquitin can influence this process. Multiple deubiquitylating enzymes (DUBs) have been implicated either in facilitating receptor endocytosis and lysosomal degradation or in rescuing receptor levels by preventing endocytosis and/or promoting recycling to the plasma membrane. In this review, we will discuss in detail what is currently known about the role of DUBs in regulating the endocytosis of various transmembrane receptors and ion channels. We will also expand upon the role DUBs play in receptor sorting at the multivesicular body to determine whether a receptor is recycled or trafficked to the lysosome for degradation. Finally, we will briefly discuss how the DUBs implicated in these processes may contribute to the pathogenesis of a range of diseases, and thus the potential these have as therapeutic targets.

Ion channnels and transporters in cancer. 5. Ion channels in control of cancer and cell apoptosis

2011 ◽  
Vol 301 (6) ◽  
pp. C1281-C1289 ◽  
Author(s):  
V'yacheslav Lehen'kyi ◽  
George Shapovalov ◽  
Roman Skryma ◽  
Natalia Prevarskaya
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Plasma Membrane ◽  
Ion Channels ◽  
Programmed Cell Death ◽  
Tissue Homeostasis ◽  
Death Rates ◽  
Cellular Processes ◽  
Regulation Of Cell Cycle

Ion channels contribute to virtually all basic cellular processes, including such crucial ones for maintaining tissue homeostasis as proliferation, differentiation, and apoptosis. The involvement of ion channels in regulation of programmed cell death, or apoptosis, has been known for at least three decades based on observation that classical blockers of ion channels can influence cell death rates, prolonging or shortening cell survival. Identification of the central role of these channels in regulation of cell cycle and apoptosis as well as the recent discovery that the expression of ion channels is not limited solely to the plasma membrane, but may also include membranes of internal compartments, has led researchers to appreciate the pivotal role of ion channels plays in development of cancer. This review focuses on the aspects of programmed cell death influenced by various ion channels and how dysfunctions and misregulations of these channels may affect the development and progression of different cancers.

scholarly journals The role of post-Golgi transport pathways and sorting motifs in the plasmodesmal targeting of the movement protein (MP) of Ourmia melon virus (OuMV)

2019 ◽  
Author(s):  
Natali Ozber ◽  
Paolo Margaria ◽  
Charles T. Anderson ◽  
Massimo Turina ◽  
Cristina Rosa
Keyword(s):  
Plasma Membrane ◽  
Movement Protein ◽  
Cell Movement ◽  
Systemic Infection ◽  
Multivesicular Body ◽  
Plant Viruses ◽  
Transport Pathways ◽  
Intracellular Targeting ◽  
Golgi Network

SummaryPlants have a highly sophisticated endomembrane system that is targeted by plant viruses for cell-to-cell movement. The movement protein (MP) of Ourmia melon virus (OuMV) is targeted to plasmodesmata (PD) and forms tubules to facilitate cell-to-cell movement. Despite a number of functionally important regions for correct subcellular localization of OuMV MP has been identified, little is known about the pathways OuMV MP hijacks to reach PD. Here, we demonstrate that OuMV MP localizes to the trans-Golgi network (TGN), but not to the multivesicular body/prevacuolar compartment or Golgi, and carries two putative sorting motifs, a tyrosine (Y) and a dileucine (LL) motif, near its N-terminus. Introducing glycine substitutions in these motifs results in loss of OuMV infectivity in Nicotiana benthamiana and Arabidopsis (Arabidopsis thaliana). Live cell imaging of GFP-labeled sorting motif mutants shows that Y motif mutants fail to localize to the TGN, plasma membrane, and PD. Mutations in the LL motif do not impair plasma membrane targeting of MP, but affect its ability to associate with callose deposits at PD. Taken together, these data suggest that both Y and LL motifs are indispensable for targeting of OuMV MP to PD and for efficient systemic infection, but show differences in functionality. This study provides new insights into the role of sorting motifs in intracellular targeting of MPs and vesicle trafficking pathways that plant viruses hijack for cell-to-cell movement.

scholarly journals When the chains do not break: the role of USP10 in physiology and pathology

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Udayan Bhattacharya ◽  
Fiifi Neizer-Ashun ◽  
Priyabrata Mukherjee ◽  
Resham Bhattacharya
Keyword(s):  
Complex Formation ◽  
Molecular Mechanisms ◽  
Protein Homeostasis ◽  
Post Translational Modification ◽  
Intracellular Protein ◽  
Lysosomal Degradation ◽  
Life Activity ◽  
Cellular Processes ◽  
Pathological Conditions

AbstractDeubiquitination is now understood to be as important as its partner ubiquitination for the maintenance of protein half-life, activity, and localization under both normal and pathological conditions. The enzymes that remove ubiquitin from target proteins are called deubiquitinases (DUBs) and they regulate a plethora of cellular processes. DUBs are essential enzymes that maintain intracellular protein homeostasis by recycling ubiquitin. Ubiquitination is a post-translational modification where ubiquitin molecules are added to proteins thus influencing activation, localization, and complex formation. Ubiquitin also acts as a tag for protein degradation, especially by proteasomal or lysosomal degradation systems. With ~100 members, DUBs are a large enzyme family; the ubiquitin-specific peptidases (USPs) being the largest group. USP10, an important member of this family, has enormous significance in diverse cellular processes and many human diseases. In this review, we discuss recent studies that define the roles of USP10 in maintaining cellular function, its involvement in human pathologies, and the molecular mechanisms underlying its association with cancer and neurodegenerative diseases. We also discuss efforts to modulate USPs as therapy in these diseases.

The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Kate Poole
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Mammalian Cells ◽  
Annual Review ◽  
Publication Date ◽  
Research Focus ◽  
Ionic Flux ◽  
Touch Sensation ◽  
Mechanical Sensing

Many aspects of mammalian physiology are mechanically regulated. One set of molecules that can mediate mechanotransduction are the mechanically activated ion channels. These ionotropic force sensors are directly activated by mechanical inputs, resulting in ionic flux across the plasma membrane. While there has been much research focus on the role of mechanically activated ion channels in touch sensation and hearing, recent data have highlighted the broad expression pattern of these molecules in mammalian cells. Disruption of mechanically activated channels has been shown to impact ( a) the development of mechanoresponsive structures, ( b) acute mechanical sensing, and ( c) mechanically driven homeostatic maintenance in multiple tissue types. The diversity of processes impacted by these molecules highlights the importance of mechanically activated ion channels in mammalian physiology. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

New Roles for Connexons

Physiology ◽  
2003 ◽  
Vol 18 (3) ◽  
pp. 100-103 ◽  
Author(s):  
Lisa Ebihara
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Gap Junction ◽  
Paracrine Signaling ◽  
Gap Junction Channels ◽  
Cellular Processes ◽  
Gap Junction Hemichannels

Connexons or gap junction hemichannels are large, nonselective ion channels that reside in the nonjunctional plasma membrane before their assembly into gap junction channels. Increasing evidence suggests that these channels can open under certain conditions and may participate in a number of cellular processes, including the release of small metabolites such as ATP and NAD+, which are involved in paracrine signaling.

scholarly journals SUMOylation in the control of cholesterol homeostasis

Open Biology ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 200054 ◽  
Author(s):  
Ana Talamillo ◽  
Leiore Ajuria ◽  
Marco Grillo ◽  
Orhi Barroso-Gomila ◽  
Ugo Mayor ◽  
...  
Keyword(s):  
Vitamin D ◽  
Plasma Membrane ◽  
Cardiovascular Diseases ◽  
Protein Modification ◽  
Cholesterol Homeostasis ◽  
Sumo Modification ◽  
Cellular Processes ◽  
Receptor Signalling ◽  
Cholesterol Levels

SUMOylation—protein modification by the small ubiquitin-related modifier (SUMO)—affects several cellular processes by modulating the activity, stability, interactions or subcellular localization of a variety of substrates. SUMO modification is involved in most cellular processes required for the maintenance of metabolic homeostasis. Cholesterol is one of the main lipids required to preserve the correct cellular function, contributing to the composition of the plasma membrane and participating in transmembrane receptor signalling. Besides these functions, cholesterol is required for the synthesis of steroid hormones, bile acids, oxysterols and vitamin D. Cholesterol levels need to be tightly regulated: in excess, it is toxic to the cell, and the disruption of its homeostasis is associated with various disorders like atherosclerosis and cardiovascular diseases. This review focuses on the role of SUMO in the regulation of proteins involved in the metabolism of cholesterol.

scholarly journals Endocytic vacuole formation by WASH-mediated endocytosis

2021 ◽  
Author(s):  
Pia Brinkert ◽  
Lena Krebs ◽  
Pilar Samperio Ventayol ◽  
Lilo Greune ◽  
Carina Bannach ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Actin Polymerization ◽  
Endocytic Pathway ◽  
Vacuole Formation ◽  
Cellular Processes ◽  
Human Papillomavirus Type 16 ◽  
Systematic Perturbation ◽  
Membrane Bending ◽  
Endocytic Pathways

Endocytosis of extracellular or plasma membrane material is a fundamental process. A variety of endocytic pathways exist, several of which are barely understood in terms of mechanistic execution and biological function. Importantly, some mechanisms have been identified and characterized by following virus internalization into cells. This includes a novel endocytic pathway exploited by human papillomavirus type 16 (HPV16). However, its cellular role and mechanism of endocytic vacuole formation remain unclear. Here, HPV16 was used as a tool to examine the mechanistic execution of vesicle formation by combining systematic perturbation of cellular processes with electron and video microscopy. Our results indicate cargo uptake by uncoated, inward-budding pits facilitated by the membrane bending retromer protein SNX2. Actin polymerization-driven vesicle scission is promoted by WASH, an actin regulator typically not found at the plasma membrane. Uncovering a novel role of WASH in endocytosis, we propose to term the new pathway WASH-mediated endocytosis (WASH-ME).

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.

Ion channels and transporters in cancer. 4. Remodeling of Ca2+ signaling in tumorigenesis: role of Ca2+ transport

2011 ◽  
Vol 301 (5) ◽  
pp. C969-C976 ◽  
Author(s):  
Jane M. Lee ◽  
Felicity M. Davis ◽  
Sarah J. Roberts-Thomson ◽  
Gregory R. Monteith
Keyword(s):  
Ion Channels ◽  
Tumor Formation ◽  
Altered Expression ◽  
Present Evidence ◽  
Cellular Processes ◽  
New Evidence

The Ca2+ signal has major roles in cellular processes important in tumorigenesis, including migration, invasion, proliferation, and apoptotic sensitivity. New evidence has revealed that, aside from altered expression and effects on global cytosolic free Ca2+ levels via direct transport of Ca2+, some Ca2+ pumps and channels are able to contribute to tumorigenesis via mechanisms that are independent of their ability to transport Ca2+ or effect global Ca2+ homeostasis in the cytoplasm. Here, we review some of the most recent studies that present evidence of altered Ca2+ channel or pump expression in tumorigenesis and discuss the importance and complexity of localized Ca2+ signaling in events critical for tumor formation.

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