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Meir Aridor
Our view of the secretory pathway has evolved from a morphological one to one that includes molecular mechanistic understanding of basic traffic components. These components include coat complexes involved in cargo sorting and budding and proteins that mediate targeting, tethering and fusion. The expanding repertoire of regulators that control basic traffic activities begins to paint a unified morphological-molecular view of secretion. The emerging picture provides key insights into the coupling of secretion with physiology...
July 6, 2018: Traffic
Divya Venkatesh, Ning Zhang, Martin Zoltner, Ricardo Canavate Del Pino, Mark C Field
The kinetoplastida and their close relatives are unicellular organisms prevalent within the eukaryotic biosphere and important for significant impacts on global health, economy and ecosystems. They are, under most models, an early branching lineage. Individual species adapted to highly diverse environments by adopting complex life styles; parasitic species can infect a wide range of eukaryotic hosts, while many relatives are free-living and some autotrophic from acquiring a plastid for photosynthesis. Adaptation is especially evident in the evolution of kinetoplastid cell surface architecture and is supported by endomembrane trafficking and serves as a platform for interaction with environment...
July 4, 2018: Traffic
Katherine Bowers, Surjit Kaila Singh Srai
Metal ion transporters of the Zrt- and Irt-like protein (ZIP, or SLC39A) family transport zinc, iron, manganese and/ or cadmium across cellular membranes and into the cytosol. The 14 human ZIP family proteins are expressed in a wide variety of tissues and function in many different cellular processes. Many of these proteins (including ZIP1, 2, 3, 4, 5, 6/10, 8, 9, 11, 12, 14) are situated, at least some of the time, on the plasma membrane, where they mediate metal ion uptake into cells. Their level on the cell surface can be controlled rapidly via protein trafficking in response to the ions they transport...
June 28, 2018: Traffic
Guan Wang, Thierry Galli
A cell is able to sense the biomechanical properties of the environment such as the rigidity of the extracellular matrix and adapt its tension via regulation of plasma membrane and underlying actomyosin meshwork properties. The cell's ability to adapt to the changing biomechanical environment is important for cellular homeostasis and also cell dynamics such as cell growth and motility. Membrane trafficking has emerged as an important mechanism to regulate cell biomechanics. In this review, we summarize the current understanding of the role of cell mechanics in exocytosis, and reciprocally, the role of exocytosis in regulating cell mechanics...
June 25, 2018: Traffic
Thomas W Kirby, Lars C Pedersen, Scott A Gabel, Natalie R Gassman, Robert E London
Despite the essential roles of pol X family enzymes in DNA repair, information about the structural basis of their nuclear import is limited. Recent studies revealed the unexpected presence of a functional NLS in DNA polymerase β, indicating the importance of active nuclear targeting, even for enzymes likely to leak into and out of the nucleus. The current studies further explore the active nuclear transport of these enzymes by identifying and structurally characterizing the functional NLS sequences in the three remaining human pol X enzymes: terminal deoxynucleotidyl transferase (TdT), DNA polymerase μ (pol μ), and DNA polymerase λ (pol λ)...
June 22, 2018: Traffic
Birol Cabukusta, Jacques Neefjes
Lysosomes are highly dynamic organelles that can move rapidly throughout the cell. They distribute in a rather immobile pool located around the microtubule-organizing center in a "cloud", and a highly dynamic pool in the cell periphery. Their spatiotemporal characteristics allow them to carry out multiple biological functions, such as cargo degradation, antigen presentation and plasma membrane repair. Therefore, it is not surprising that lysosomal dysfunction underlies various diseases, including cancer, neurodegenerative and autoimmune diseases...
June 14, 2018: Traffic
Theodore L Steck, Yvonne Lange
The transverse asymmetry (sidedness) of phospholipids in plasma membrane bilayers is well characterized, distinctive, actively maintained and functionally important. In contrast, numerous studies using a variety of techniques have concluded that plasma membrane bilayer cholesterol is either mostly in the outer leaflet or the inner leaflet or is fairly evenly distributed. Sterols might simply partition according to their differing affinities for the asymmetrically-disposed phospholipids, but some studies have proposed that it is actively transported to the outer leaflet...
June 13, 2018: Traffic
Michael Ritt, Sivaraj Sivaramakrishnan
While unconventional myosins interact with different stages of the endocytic pathway, they are ascribed a transport function that is secondary to the protein complexes that control organelle identity. Endosomes are subject to a dynamic, continuous flux of proteins that control their characteristic properties, including their motility within the cell. Efforts to describe the changes in identity of this compartment have largely focused on the adaptors present on the compartment and not on the motile properties of the compartment itself...
June 4, 2018: Traffic
Maciej K Rogacki, Ottavia Golfetto, Steven J Tobin, Tianyi Li, Sunetra Biswas, Raphael Jorand, Huiying Zhang, Vlad Radoi, Yu Ming, Per Svenningsson, Daniel Ganjali, Devin L Wakefield, Athanasios Sideris, Alexander R Small, Lars Terenius, Tijana Jovanović-Talisman, Vladana Vukojević
Opioid receptors are important pharmacological targets for the management of numerous medical conditions (eg, severe pain), but they are also the gateway to the development of deleterious side effects (eg, opiate addiction). Opioid receptor signaling cascades are well characterized. However, quantitative information regarding their lateral dynamics and nanoscale organization in the plasma membrane remains limited. Since these dynamic properties are important determinants of receptor function, it is crucial to define them...
May 28, 2018: Traffic
Cayla E Jewett, Rytis Prekeris
The creation of cellular tubes is one of the most vital developmental processes, resulting in the formation of most organ types. Cells have co-opted a number of different mechanisms for tube morphogenesis that vary among tissues and organisms; however, generation and maintenance of cell polarity is fundamental for successful lumenogenesis. Polarized membrane transport has emerged as a key driver not only for establishing individual epithelial cell polarity, but also for coordination of epithelial polarization during apical lumen formation and tissue morphogenesis...
May 16, 2018: Traffic
Luis-Carlos Tábara, Juan-Jesús Vicente, Joanna Biazik, Eeva-Liisa Eskelinen, Olivier Vincent, Ricardo Escalante
The multispanning membrane protein vacuole membrane protein 1 (VMP1) marks and regulates endoplasmic reticulum (ER)-domains associated with diverse ER-organelle membrane contact sites. A proportion of these domains associate with endosomes during their maturation and remodeling. We found that these VMP1 domains are enriched in choline/ethanolamine phosphotransferase and phosphatidylinositol synthase (PIS1), 2 ER enzymes required for the synthesis of various phospholipids. Interestingly, the lack of VMP1 impairs the formation of PIS1-enriched ER domains, suggesting a role in the distribution of phosphoinositides...
May 14, 2018: Traffic
Yi Xie, Hui Miao, J Todd Blankenship
Our understanding of how membrane trafficking pathways function to direct morphogenetic movements and the planar polarization of developing tissues is a new and emerging field. While a central focus of developmental biology has been on how protein asymmetries and cytoskeletal force generation direct cell shaping, the role of membrane trafficking in these processes has been less clear. Here, we review recent advances in Drosophila and vertebrate systems in our understanding of how trafficking events are coordinated with planar cytoskeletal function to drive lasting changes in cell and tissue topologies...
May 14, 2018: Traffic
Anthony R Mele, Jamie Marino, Kenneth Chen, Vanessa Pirrone, Chris Janetopoulos, Brian Wigdahl, Zachary Klase, Michael R Nonnemacher
The human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) protein functions both intracellularly and extracellularly. Intracellularly the main function is to enhance transcription of the viral promoter. However, this process only requires a small amount of intracellular Tat. The majority of Tat is secreted through an unconventional mechanism by binding to phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2 ), a phospholipid in the inner leaflet of the plasma membrane that is required for secretion...
April 30, 2018: Traffic
Sarah C Charnaud, Thorey K Jonsdottir, Paul R Sanders, Hayley E Bullen, Benjamin K Dickerman, Betty Kouskousis, Catherine S Palmer, Halina M Pietrzak, Annamarie E Laumaea, Anna-Belen Erazo, Emma McHugh, Leann Tilley, Brendan S Crabb, Paul R Gilson
Plasmodium falciparum, which causes malaria, extensively remodels its human host cells, particularly erythrocytes. Remodelling is essential for parasite survival by helping to avoid host immunity and assisting in the uptake of plasma nutrients to fuel rapid growth. Host cell renovation is carried out by hundreds of parasite effector proteins that are exported into the erythrocyte across an enveloping parasitophorous vacuole membrane (PVM). The Plasmodium translocon for exported (PTEX) proteins is thought to span the PVM and provide a channel that unfolds and extrudes proteins across the PVM into the erythrocyte...
April 26, 2018: Traffic
Stella M Lu, Gregory D Fairn
The plasma membrane is inhomogeneously organized containing both highly ordered and disordered nanodomains. 7-Ketocholesterol (7KC), an oxysterol formed from the nonenzymatic oxidation of cholesterol, is a potent disruptor of membrane order. Importantly, 7KC is a component of oxidized low-density lipoprotein and accumulates in macrophage and foam cells found in arterial plaques. Using a murine macrophage cell line, J774, we report that both IgG-mediated and phosphatidylserine-mediated phagocytic pathways are inhibited by the accumulation of 7KC...
April 24, 2018: Traffic
Michael W Hess, Georg F Vogel, Teodor E Yordanov, Barbara Witting, Karin Gutleben, Hannes L Ebner, Mariana E G de Araujo, Przemyslaw A Filipek, Lukas A Huber
Immunogold labeling of permeabilized whole-mount cells or thin-sectioned material is widely used for the subcellular localization of biomolecules at the high spatial resolution of electron microscopy (EM). Those approaches are well compatible with either 3-dimensional (3D) reconstruction of organelle morphology and antigen distribution or with rapid cryofixation-but not easily with both at once. We describe here a specimen preparation and labeling protocol for animal cell cultures, which represents a novel blend of specifically adapted versions of established techniques...
April 19, 2018: Traffic
Rebecca L Adams, Aaron C Mason, Laura Glass, Aditi, Susan R Wente
No abstract text is available yet for this article.
August 2018: Traffic
Dakota J Brock, Lauren Kustigian, Mengqiu Jiang, Kristin Graham, Ting-Yi Wang, Alfredo Erazo-Oliveras, Kristina Najjar, Junjie Zhang, Hays Rye, Jean-Philippe Pellois
Various densely charged polycationic species, whether of biological or synthetic origin, can penetrate human cells, albeit with variable efficiencies. The molecular underpinnings involved in such transport remain unclear. Herein, we assemble 1, 2 or 3 copies of the HIV peptide TAT on a synthetic scaffold to generate branched cell-permeable prototypes with increasing charge density. We establish that increasing TAT copies dramatically increases the cell penetration efficiency of the peptides while simultaneously enabling the efficient cytosolic delivery of macromolecular cargos...
June 2018: Traffic
Khan Umaer, Peter J Bush, James D Bangs
Trypanosoma brucei possesses a streamlined secretory system that guarantees efficient delivery to the cell surface of the critical glycosyl-phosphatidylinositol (GPI)-anchored virulence factors, variant surface glycoprotein (VSG) and transferrin receptor (TfR). Both are thought to be constitutively endocytosed and returned to the flagellar pocket via TbRab11+ recycling endosomes. We use conditional knockdown with established reporters to investigate the role of TbRab11 in specific endomembrane trafficking pathways in bloodstream trypanosomes...
June 2018: Traffic
Jessica B Blackburn, Tetyana Kudlyk, Irina Pokrovskaya, Vladimir V Lupashin
The conserved oligomeric Golgi (COG) complex controls membrane trafficking and ensures Golgi homeostasis by orchestrating retrograde vesicle trafficking within the Golgi. Human COG defects lead to severe multisystemic diseases known as COG-congenital disorders of glycosylation (COG-CDG). To gain better understanding of COG-CDGs, we compared COG knockout cells with cells deficient to 2 key enzymes, Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase and uridine diphosphate-glucose 4-epimerase (GALE), which contribute to proper N- and O-glycosylation...
June 2018: Traffic
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