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Cellular trafficking

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https://www.readbyqxmd.com/read/29053845/substitution-of-yor1p-nbd1-residues-improves-the-thermal-stability-of-human-cystic-fibrosis-transmembrane-conductance-regulator
#1
B M Xavier, E Hildebrandt, F Jiang, H Ding, J C Kappes, I L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a plasma membrane chloride channel protein that regulates vertebrate fluid homeostasis. The inefficiency of wild type human CFTR protein folding/trafficking is exacerbated by genetic mutations that can cause protein misfolding in the endoplasmic reticulum (ER) and subsequent degradation. This project investigates small changes in protein sequence that can alter the thermal stability of the large multi-domain CFTR protein. We target a conserved 70-residue α-subdomain located in the first nucleotide-binding domain that hosts the common misfolding mutation ∆F508...
October 19, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29052144/the-effects-of-extracellular-serum-concentration-on-app-processing-in-npc1-deficient-app-overexpressing-n2a-cells
#2
M Maulik, D Vergote, G Phukan, J Chung, G Thinakaran, S Kar
Amyloid precursor protein (APP) is cleaved by a set of proteases including α-/β-/γ- and recently identified η-secretases, generating C-terminal fragments (CTFs) of varying lengths and amyloid β (Aβ) peptides, which are considered to play a pivotal role in Alzheimer's disease (AD) pathogenesis. Cellular cholesterol content/distribution can regulate the production/clearance of APP metabolites and hence modify AD pathology. To determine the functional relation between endosomal-lysosomal (EL) cholesterol sequestration and APP metabolism, we used our recently developed mouse N2a-ANPC cells that overexpress Swedish mutant human APP in the absence of cholesterol-trafficking Niemann-Pick type C1 (Npc1) protein...
October 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29046458/a-tyrosine-based-trafficking-motif-of-the-tegument-protein-pul71-is-crucial-for-human-cytomegalovirus-secondary-envelopment
#3
Andrea N Dietz, Clarissa Villinger, Stefan Becker, Manfred Frick, Jens von Einem
The human cytomegalovirus (HCMV) tegument protein pUL71 is required for efficient secondary envelopment and accumulates at the Golgi-derived viral assembly complex (vAC) during infection. Analysis of various C-terminally truncated pUL71 fused to eGFP identified amino acids 23-34 as important determinants for its Golgi localization. Sequence analysis and mutational verification revealed the presence of an N-terminal tyrosine-based trafficking motif (YxxΦ) in pUL71. This led us to hypothesize a requirement of the YxxΦ motif for the function of pUL71 in infection...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29043684/imaging-the-er-and-endomembrane-system-in-cereal-endosperm
#4
Verena Ibl, Jenny Peters, Eva Stöger, Elsa Arcalís
The cereal endosperm is a complex structure comprising distinct cell types, characterized by specialized organelles for the accumulation of storage proteins. Protein trafficking in these cells is complicated by the presence of several different storage organelles including protein bodies (PBs) derived from the endoplasmic reticulum (ER) and dynamic protein storage vacuoles (PSVs). In addition, trafficking may follow a number of different routes depending on developmental stage, showing that the endomembrane system is capable of massive reorganization...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043683/fluorescence-imaging-of-autophagy-mediated-er-to-vacuole-trafficking-in-plants
#5
Hadas Peled-Zehavi, Gad Galili
Macroautophagy (hereafter referred to as autophagy) is a conserved mechanism in eukaryotic cells that delivers unneeded cellular components for degradation in the lytic organelle. In plants, as in other eukaryotes, autophagy begins in the formation of cup-shaped double membranes that engulf cytosolic material. The double membrane closes to form autophagosomes that are then transported to the vacuole for degradation. Autophagy can function as a bulk nonselective process or as a selective process targeting specific proteins, protein aggregates, organelles, or other cellular components for degradation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043503/pharmacoperones-for-misfolded-gonadotropin-receptors
#6
Claire L Newton, Ross C Anderson
The gonadotropin receptors (luteinising hormone receptor; LHR and follicle-stimulating hormone receptor; FSHR) are G protein-coupled receptors (GPCRs) that play an important role in the endocrine control of reproduction. Thus genetic mutations that cause impaired function of these receptors have been implicated in a number of reproductive disorders. Disease-causing genetic mutations in GPCRs frequently result in intracellular retention and degradation of the nascent protein through misfolding and subsequent recognition by cellular quality control machinery...
October 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29042548/human-mesenchymal-stromal-cells-transplanted-into-mice-stimulate-renal-tubular-cells-and-enhance-mitochondrial-function
#7
Luca Perico, Marina Morigi, Cinzia Rota, Matteo Breno, Caterina Mele, Marina Noris, Martino Introna, Chiara Capelli, Lorena Longaretti, Daniela Rottoli, Sara Conti, Daniela Corna, Giuseppe Remuzzi, Ariela Benigni
Mesenchymal stromal cells (MSCs) are renoprotective and drive regeneration following injury, although cellular targets of such an effect are still ill-defined. Here, we show that human umbilical cord (UC)-MSCs transplanted into mice stimulate tubular cells to regain mitochondrial mass and function, associated with enhanced microtubule-rich projections that appear to mediate mitochondrial trafficking to create a reparative dialogue among adjacent tubular cells. Treatment with UC-MSCs in mice with cisplatin-induced acute kidney injury (AKI) regulates mitochondrial biogenesis in proximal tubuli by enhancing PGC1α expression, NAD(+) biosynthesis and Sirtuin 3 (SIRT3) activity, thus fostering antioxidant defenses and ATP production...
October 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29042286/protein-kinase-and-lipase-inhibitors-of-inositide-metabolism-deplete-ip7-indirectly-in-pancreatic-%C3%AE-cells-off-target-effects-on-cellular-bioenergetics-and-direct-effects-on-ip6k-activity
#8
Subu Surendran Rajasekaran, Christopher Illies, Stephen B Shears, Huanchen Wang, Thais S Ayala, Joilson O Martins, Elisabetta Daré, Per-Olof Berggren, Christopher J Barker
Inositol pyrophosphates have emerged as important regulators of many critical cellular processes from vesicle trafficking and cytoskeletal rearrangement to telomere length regulation and apoptosis. We have previously demonstrated that 5-di-phosphoinositol pentakisphosphate, IP7, is at a high level in pancreatic β-cells and is important for insulin exocytosis. To better understand IP7 regulation in β-cells, we used an insulin secreting cell line, HIT-T15, to screen a number of different pharmacological inhibitors of inositide metabolism for their impact on cellular IP7...
October 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29039124/recent-progress-in-mass-spectrometry-proteomics-for-biomedical-research
#9
REVIEW
Xu Li, Wenqi Wang, Junjie Chen
Proteins are the key players in many cellular processes. Their composition, trafficking, and interactions underlie the dynamic processes of life. Furthermore, diseases are frequently accompanied by malfunction of proteins at multiple levels. Understanding how biological processes are regulated at the protein level is critically important to understanding the molecular basis for diseases and often shed light on disease prevention, diagnosis, and treatment. With rapid advances in mass spectrometry (MS) instruments and experimental methodologies, MS-based proteomics has become a reliable and essential tool for elucidating biological processes at the protein level...
October 13, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29038303/f-actin-reorganization-by-v-atpase-inhibition-in-prostate-cancer
#10
Yamhilette Licon-Munoz, Vera Michel, Colleen A Fordyce, Karlett J Parra
The vacuolar ATPase (V-ATPase) proton pump sustains cellular pH homeostasis, and its inhibition triggers numerous stress responses. However, the cellular mechanisms involved remain largely elusive in cancer cells. We studied V-ATPase in the prostate cancer (PCa) cell line PC-3, which has characteristics of highly metastatic PCa. V-ATPase inhibitors impaired endo-lysosomal pH, vesicle trafficking, migration, and invasion. V-ATPase accrual in the Golgi and recycling endosomes suggests that traffic of internalized membrane vesicles back to the plasma membrane was particularly impaired...
October 16, 2017: Biology Open
https://www.readbyqxmd.com/read/29038230/ghrelin-receptor-constitutive-activity-reduces-surface-expression-of-voltage-gated-calcium-channels-in-a-cav%C3%AE-dependent-manner
#11
Emilio R Mustafá, Eduardo J López Soto, Valentina Martínez Damonte, Silvia S Rodríguez, Diane Lipscombe, Jesica Raingo
Voltage gated calcium (CaV) channels couple membrane depolarization to calcium influx, triggering a range of calcium-dependent cellular processes. CaV channels are therefore critical in shaping neuronal activity and function, depending on their individual temporal and spatial properties. Furthermore, many neurotransmitters and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal activity by altering the expression, trafficking, or function of CaV channels. GPCR-dependent mechanisms that down regulate CaV channel expression levels are observed in many neurons but are, by comparison, less studied...
October 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29036428/exocyst-exosomes-and-autophagy-in-the-regulation-of-brassicaceae-pollen-stigma-interactions
#12
Daphne R Goring
Brassicaceae pollen-stigma interactions have been extensively studied in Brassica and Arabidopsis species to identify cellular events triggered in the stigmatic papillae by pollen contact. Compatible pollinations are linked to the activation of basal cellular responses in the stigmatic papillae, which include calcium gradients, actin networks, and polarized secretion. The occurrence of these cellular events in stigmatic papillae coincides with the stages of pollen hydration and pollen tube entry into the stigmatic papillar cell wall...
September 27, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29036179/extreme-strontium-concentrations-reveal-specific-biomineralization-pathways-in-certain-coccolithophores-with-implications-for-the-sr-ca-paleoproductivity-proxy
#13
Michaël Hermoso, Benjamin Lefeuvre, Fabrice Minoletti, Marc de Rafélis
The formation of the coccolith biominerals by a group of marine algae (the Coccolithophores) offers fascinating research avenues both from the biological and geological sides. It is surprising how biomineralisation by a key phytoplanktonic group remains underconstrained, yet is influential on ocean alkalinity and responsible for the built up of our paleoclimatic archive over the last 200 Myrs. Here, we report two close relative coccolith taxa exhibiting substantial bioaccumulation of strontium: Scyphosphaera and Pontosphaera grown in the laboratory or retrieved from Pliocene sediments...
2017: PloS One
https://www.readbyqxmd.com/read/29034219/rab-gtpases-in-immunity-and-inflammation
#14
REVIEW
Akriti Prashar, Laura Schnettger, Elliott M Bernard, Maximiliano G Gutierrez
Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking. In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation.
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29033963/convergent-evolution-of-pathogen-effectors-toward-reactive-oxygen-species-signaling-networks-in-plants
#15
REVIEW
Nam-Soo Jwa, Byung Kook Hwang
Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29033361/binding-of-pld2-generated-phosphatidic-acid-to-kif5b-promotes-mt1-mmp-surface-trafficking-and-lung-metastasis-of-mouse-breast-cancer-cells
#16
Ziqing Wang, Feng Zhang, Jingquan He, Ping Wu, Li Wei Rachel Tay, Ming Cai, Weiqi Nian, Yuanyuan Weng, Li Qin, Jeffrey T Chang, Laura B McIntire, Gilbert Di Paolo, Jianming Xu, Junmin Peng, Guangwei Du
Little is known about the cellular events promoting metastasis. We show that knockout of phospholipase D2 (PLD2), which generates the signaling lipid phosphatidic acid (PA), inhibits lung metastases in the mammary tumor virus (MMTV)-Neu transgenic mouse breast cancer model. PLD2 promotes local invasion through the regulation of the plasma membrane targeting of MT1-MMP and its associated invadopodia. A liposome pull-down screen identifies KIF5B, the heavy chain of the motor protein kinesin-1, as a new PA-binding protein...
October 11, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29032537/analysis-of-lipids-and-lipid-rafts-in-borrelia
#17
Alvaro Toledo, Zhen Huang, Jorge L Benach, Erwin London
Lipid rafts are membrane microdomains that are involved in cellular processes such as protein trafficking and signaling processes, and which play a fundamental role in membrane fluidity and budding. The lipid composition of the membrane and the biochemical characteristics of the lipids found within rafts define the ability of cells to form microdomains and compartmentalize the membrane. In this chapter, we describe the biophysical, biochemical, and molecular approaches used to define and characterize lipid rafts in the Lyme disease agent, Borrelia burgdorferi...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29032301/formation-of-asymmetric-vesicles-via-phospholipase-d-mediated-transphosphatidylation
#18
Rina Takaoka, Haruko Kurosaki, Hiroyuki Nakao, Keisuke Ikeda, Minoru Nakano
Most biomembranes have an asymmetric structure with regard to phospholipid distribution between the inner and outer leaflets of the lipid bilayers. Control of the asymmetric distribution plays a pivotal role in several cellular functions such as intracellular membrane fusion and cell division. The mechanism by which membrane asymmetry and its alteration function in these transformation processes is not yet clear. To understand the significance of membrane asymmetry on trafficking and metabolism of intracellular vesicular components, a system that experimentally reproduces the asymmetric nature of biomembranes is essential...
October 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29032193/selenium-functionalized-liposomes-for-systemic-delivery-of-doxorubicin-with-enhanced-pharmacokinetics-and-anticancer-effect
#19
Qian Xie, Wenji Deng, Xue Yuan, Huan Wang, Zhiguo Ma, Baojian Wu, Xingwang Zhang
Liposomes have shown to be an excellent drug delivery system, but the short in vivo fate discourages their popularity. This work aimed to develop selenium-functionalized liposomes (SeLPs) for doxorubicin (Dox) delivery to prolong the systemic circulation of liposomes by in situ selenium coating and enhance the anticancer effect via the synergy between Dox and selenium. Dox-loaded SeLPs (Dox-SeLPs) were prepared by film hydration/active loading/in situ reduction technique and characterized by particle size, entrapment efficiency and morphology...
October 12, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29031163/ebola-virus-requires-phosphatidylinositol-3-5-bisphosphate-production-for-efficient-viral-entry
#20
Shirley Qiu, Anders Leung, Yuxia Bo, Robert A Kozak, Sai Priya Anand, Corina Warkentin, Fabiola D R Salambanga, Jennifer Cui, Gary Kobinger, Darwyn Kobasa, Marceline Côté
For entry, Ebola virus (EBOV) requires the interaction of its viral glycoprotein with the cellular protein Niemann-Pick C1 (NPC1) which resides in late endosomes and lysosomes. How EBOV is trafficked and delivered to NPC1 and whether this is positively regulated during entry remain unclear. Here, we show that the PIKfyve-ArPIKfyve-Sac3 cellular complex, which is involved in the metabolism of phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), is critical for EBOV infection. Although the expression of all subunits of the complex was required for efficient entry, PIKfyve kinase activity was specifically critical for entry by all pathogenic filoviruses...
October 11, 2017: Virology
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