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membrane trafficking

Adrian J Giovannone, Elena Reales, Pallavi Bhattaram, Alberto Fraile-Ramos, Thomas Weimbs
The uptake and trafficking of cell surface receptors can be monitored by a technique called 'antibody-feeding' which uses an externally applied antibody to label the receptor on the surface of cultured, live cells. Here, we adapt the traditional antibody-feeding experiment to polarized epithelial cells (Madin-Darby Canine Kidney) grown on permeable Transwell supports. By adding two tandem extracellular Myc epitope tags to the C-terminus of the SNARE protein syntaxin 3 (Stx3), we provided a site where an antibody could bind, allowing us to perform antibody-feeding experiments on cells with distinct apical and basolateral membranes...
February 5, 2018: Bio-protocol
Zhe Yang, Jordan Follett, Markus C Kerr, Thomas Clairfeuille, Mintu Chandra, Brett M Collins, Rohan D Teasdale
The Alanine, Serine, Cysteine-preferring Transporter 2 (ASCT2; SLC1A5) is responsible for the uptake of glutamine into cells, a major source of cellular energy and a key regulator of mammalian Target of Rapamycin (mTOR) activation. Furthermore, ASCT2 expression has reported in several human cancers making it a potential target for both diagnostic and therapeutic purposes. Here we identify ASCT2 as a membrane trafficked cargo molecule, sorted through a direct interaction with the PDZ domain of Sorting Nexin 27 (SNX27)...
March 21, 2018: Journal of Biological Chemistry
Claudia Cavallini, Chiara Zannini, Elena Olivi, Riccardo Tassinari, Valentina Taglioli, Martina Rossi, Paola Poggi, Alexandros Chatgilialoglu, Giuliana Simonazzi, Francesco Alviano, Laura Bonsi, Carlo Ventura
Human mesenchymal stem cells (hMSCs) are an effective tool in regenerative medicine notably for their intrinsic plentiful paracrine activity rather than differentiating properties. The hMSC secretome includes a wide spectrum of regulatory and trophic factors, encompassing several naked molecules as well as different kinds of extracellular vesicles (EVs). Among EVs, exosomes represent an intriguing population, able to shuttle proteins, transcription factors, and genetic materials, with a relevant role in cell-to-cell communication, modulating biological responses in recipient cells...
January 2018: Cell Transplantation
Abigail K Corona, Holly M Saulsbery, Angel F Corona Velazquez, William T Jackson
Enterovirus D68 (EV-D68) is a medically important respiratory plus-strand RNA virus of children that has been linked to acute flaccid myelitis. We have determined that EV-D68 induces autophagic signaling and membrane formation. Autophagy, a homeostatic degradative process that breaks down protein aggregates and damaged organelles, promotes replication of multiple plus-strand viruses. Induction of autophagic signals promotes EV-D68 replication, but the virus inhibits the downstream degradative steps of autophagy in multiple ways...
March 20, 2018: Cell Reports
Liansheng Liu, Jinqiu Lu, Xiaoling Li, Ailing Wu, Qingzhe Wu, Mujun Zhao, Nan Tang, Hai Song
Intracellular transport of membranous organelles and protein complexes to various destinations is fundamental to signaling transduction and cellular function. The cytoplasmic dynein motor and its regulatory proteins LIS1 and NDE1 are required for transporting a variety of cellular cargos along the microtubule network. In this study, we show that deletion of Lis1 in developing lung endoderm and limb mesenchymal cells causes agenesis of the lungs and limbs. In both mutants, there is increased cell death and decreased fibroblast growth factor (FGF) signaling activity...
March 20, 2018: Cell Reports
Wuxing Dong, Alison C Todd, Angelika Bröer, Sarah R Hulme, Stefan Bröer, Brian Billups
Astrocytes are glial cells that have an intimate physical and functional association with synapses in the brain. One of their main roles is to recycle the neurotransmitters glutamate and gamma-aminobutyric acid (GABA), as a component of the glutamate/GABA-glutamine cycle. They perform this function by sequestering neurotransmitters and releasing glutamine via the neutral amino acid transporter SNAT3. In this way, astrocytes regulate the availability of neurotransmitters and subsequently influence synaptic function...
March 21, 2018: International Journal of Molecular Sciences
Robert D Guber, Alice B Schindler, Maher S Budron, Ke-Lian Chen, Yuebing Li, Kenneth H Fischbeck, Christopher Grunseich
Amyotrophic lateral sclerosis 8 (ALS8) is a rare progressive neurodegenerative disease resulting from mutation in the gene for vesicle-associated membrane protein-associated protein B. We evaluated a North American patient using exome sequencing, and identified a P56S mutation. The disease protein had similar subcellular localization and expression levels in the patient and control fibroblasts. Patient fibroblasts showed increased basal endoplasmic reticulum stress and dysfunction of nucleocytoplasmic transport as evidenced by impaired Ran trafficking...
March 2018: Annals of Clinical and Translational Neurology
Anish Sharda, Robert Flaumenhaft
Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways...
2018: F1000Research
Ralph Witzgall
Primary cilia represent small, yet distinct compartments of the plasma membrane. They are speculated to exercise chemo- and mechanosensory functions and to serve as signaling hubs for crucial pathways such as the Wnt and hedgehog cascades. It is therefore necessary that specific integral membrane proteins, in particular sensors and receptors, are sorted to the cilium and not to the surrounding somatic plasma membrane upon being synthesized at the rough endoplasmic reticulum. Apparently no singular "zip code" for the primary cilium exists but rather several ciliary targeting signals whose biochemical and cell biological implications are just about being unravelled...
March 17, 2018: Seminars in Cell & Developmental Biology
Helder Rocha, André F Maia, Reto Gassmann
Cytoplasmic dynein 1 (dynein) is the predominant microtubule minus end-directed motor in animals and participates in a wide range of cellular processes, including membrane trafficking, nuclear migration, and cell division. Dynein's functional diversity depends on co-factors that regulate its subcellular localization, interaction with cargo, and motor activity. The ubiquitous co-factor nuclear distribution gene E (NudE) is implicated in many of dynein's functions, and mutations in NudE cause the brain developmental disease microcephaly...
March 20, 2018: Scientific Data
Daniel Mattle, Bernd Kuhn, Johannes Aebi, Marc Bedoucha, Demet Kekilli, Nathalie Grozinger, Andre Alker, Markus G Rudolph, Georg Schmid, Gebhard F X Schertler, Michael Hennig, Jörg Standfuss, Roger J P Dawson
In the degenerative eye disease retinitis pigmentosa (RP), protein misfolding leads to fatal consequences for cell metabolism and rod and cone cell survival. To stop disease progression, a therapeutic approach focuses on stabilizing inherited protein mutants of the G protein-coupled receptor (GPCR) rhodopsin using pharmacological chaperones (PC) that improve receptor folding and trafficking. In this study, we discovered stabilizing nonretinal small molecules by virtual and thermofluor screening and determined the crystal structure of pharmacologically stabilized opsin at 2...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Sophie Brameyer, Laure Plener, Axel Müller, Andreas Klingl, Gerhard Wanner, Kirsten Jung
Many bacteria use extracellular signaling molecules to coordinate group behavior, a process referred to as quorum sensing (QS). However, some QS molecules are hydrophobic in character and are probably unable to diffuse across the bacterial cell envelope. How these molecules are disseminated between bacterial cells within a population is not yet fully understood. Here we show that the marine pathogen Vibrio harveyi packages the hydrophobic QS molecule CAI-1, a long-chain amino ketone, into outer membrane vesicles...
March 19, 2018: Journal of Bacteriology
Mandy Berndt-Paetz, Luise Herbst, Annett Weimann, Andreas Gonsior, Jens-Uwe Stolzenburg, Jochen Neuhaus
PURPOSE: Muscarinic acetylcholine receptors (mAChRs) regulate a number of important physiological functions. Alteration of mAChR expression or function has been associated in the etiology of several pathologies including functional bladder disorders (e.g bladder pain syndrome/interstitial cystitis - BPS/IC). In a previous study we found specific mAChR expression patterns associated with BPS/IC, while correlation between protein and gene expression was lacking. Posttranslational regulatory mechanisms, e...
March 15, 2018: Acta Histochemica
Sohail Raza, Gualtiero Alvisi, Farzana Shahin, Urooj Husain, Masood Rabbani, Tahir Yaqub, Aftab Ahmad Anjum, Ali Ahmad Sheikh, Muhammad Nawaz, Muhammad Asad Ali
Most enveloped viruses exploit complex cellular pathways for assembly and egress from the host cell, and the large DNA virus Herpes simplex virus 1 (HSV-1) makes no exception, hijacking several cellular transport pathways for its glycoprotein trafficking and maturation, as well as for viral morphogenesis and egress according to the envelopment, de-envelopment and re-envelopment model. Importantly Rab GTPases, widely distributed master regulators of intracellular membrane trafficking pathways, have recently being tightly implicated in such process...
March 15, 2018: Microbial Pathogenesis
Maria S Shutova, Tatyana M Svitkina
Nonmuscle myosin II is an actin-based motor that executes numerous mechanical tasks in cells including spatiotemporal organization of the actin cytoskeleton, adhesion, migration, cytokinesis, tissue remodeling, and membrane trafficking. Nonmuscle myosin II is ubiquitously expressed in mammalian cells as a tissue-specific combination of three paralogs. Recent studies reveal novel specific aspects of their kinetics, intracellular regulation and functions. On the other hand, the three paralogs also can copolymerize and cooperate in cells...
March 16, 2018: Biochemical and Biophysical Research Communications
Janelle L Harris, Keyur Dave, Jeffrey Gorman, Kum Kum Khanna
BACKGROUND AND AIMS: 5T4 is a transmembrane glycoprotein with limited expression in normal adult tissues and expression in some solid tumours. It is unclear whether 5T4 is preferentially expressed by stem or differentiated cell types. Modes of 5T4 regulation are unknown despite its ongoing development as a cancer immunotherapy target. Our aims were to clarify the differentiation status of 5T4 expressing cells in breast cancer and to understand the mechanism underlying 5T4 membrane presentation...
March 13, 2018: International Journal of Biochemistry & Cell Biology
Aaron Scholl, Yuyang Yang, Patrick McBride, Kelly Irwin, Lan Jiang
The Drosophila trachea is a premier genetic system to investigate the fundamental mechanisms of tubular organ formation. Development of the trachea consists of the well understood early branch specification and migration processes, and the less clear later branch maturation process including the apical membrane expansion, cytoskeleton rearrangement, luminal matrix clearance, and air-filling. We identified seven members of the Osiris (Osi) gene family with obvious tracheal expression in trachea. In addition, HA-tagged Osi proteins are highly concentrated in vesicle-like structures at and near the apical membrane...
March 13, 2018: Gene Expression Patterns: GEP
Binyong Liang, Lukas K Tamm
SNARE-mediated membrane fusion is a ubiquitous process responsible for intracellular vesicle trafficking, including membrane fusion in exocytosis that leads to hormone and neurotransmitter release. The proteins that facilitate this process are highly dynamic and adopt multiple conformations when they interact with other proteins and lipids as they form highly regulated molecular machines that operate on membranes. Solution NMR is an ideal method to capture high-resolution glimpses of the molecular transformations that take place when these proteins come together and work on membranes...
April 2018: Progress in Nuclear Magnetic Resonance Spectroscopy
Da-Zhi Guo, Lin Xiao, Yi-Jun Liu, Chen Shen, Hui-Fang Lou, Yan Lv, Shu-Yi Pan
This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells...
March 16, 2018: Experimental & Molecular Medicine
Joseph E Pick, Edward B Ziff
A fundamental property of the brain is its ability to modify its function in response to its own activity. This ability for self-modification depends to a large extent on synaptic plasticity. It is now appreciated that for excitatory synapses, a significant part of synaptic plasticity depends upon changes in the post synaptic response to glutamate released from nerve terminals. Modification of the post synaptic response depends, in turn, on changes in the abundances of AMPA receptors in the post synaptic membrane...
March 12, 2018: Molecular and Cellular Neurosciences
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