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https://www.readbyqxmd.com/read/29212874/the-na-k-h-exchanger-nhx1-controls-multivesicular-body-vacuolar-lysosome-fusion
#1
Mahmoud Abdul Karim, Christopher Leonard Brett
Loss-of-function mutations in human endosomal Na+(K+)/H+ Exchangers (NHEs) NHE6 and NHE9 are implicated in neurological disorders including Christianson Syndrome, autism and attention deficit and hyperactivity disorder (ADHD). These mutations disrupt retention of surface receptors within neurons and glial cells by affecting their delivery to lysosomes for degradation. However, the molecular basis of how these endosomal NHEs control endocytic trafficking is unclear. Using Saccharomyces cerevisiae as a model, we conducted cell-free organelle fusion assays to show that transport activity of the orthologous endosomal NHE Nhx1 is important for multivesicular body (MVB)-vacuolar lysosome fusion, the last step of endocytosis required for surface protein degradation...
December 6, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29212659/unconventional-secretion-of-fabp4-by-endosomes-and-secretory-lysosomes
#2
Julien Villeneuve, Laia Bassaganyas, Sebastien Lepreux, Marioara Chiritoiu, Pierre Costet, Jean Ripoche, Vivek Malhotra, Randy Schekman
An appreciation of the functional properties of the cytoplasmic fatty acid binding protein 4 (FABP4) has advanced with the recent demonstration that an extracellular form secreted by adipocytes regulates a wide range of physiological functions. Little, however, is known about the mechanisms that mediate the unconventional secretion of FABP4. Here, we demonstrate that FABP4 secretion is mediated by a membrane-bounded compartment, independent of the conventional endoplasmic reticulum-Golgi secretory pathway. We show that FABP4 secretion is also independent of GRASP proteins, autophagy, and multivesicular bodies but involves enclosure within endosomes and secretory lysosomes...
December 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29210491/multicompartment-vesicles-formation-by-emulsification-induced-assembly-of-poly-ethylene-oxide-block-poly-%C3%AE%C2%B5-caprolactone-and-their-dual-loading-capability
#3
Seon-Mi Jin, Jongseol Jeon, Mi-Kyoung Park, Geon Hee Kim, Eunji Lee
Emulsification-induced assembly is employed to allow structural diversity in nanoaggregates of a biocompatible amphiphilic polymer, poly(ethylene oxide)-block-poly(ε-caprolactone). Onion-like vesicles are efficiently produced by tuning the interfacial instability of the oil-in-water emulsion. The increase in the polymer concentration and use of the organic solvents with a low interfacial tension between water and the oil phase lead to a strong tendency of emulsion droplets to generate the onion-like vesicles...
December 6, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/29198173/autophagy-inhibition-promotes-snca-alpha-synuclein-release-and-transfer-via-extracellular-vesicles-with-a-hybrid-autophagosome-exosome-like-phenotype
#4
Georgia Minakaki, Stefanie Menges, Agnes Kittel, Evangelia Emmanouilidou, Iris Schaeffner, Katalin Barkovits, Anna Bergmann, Edward Rockenstein, Anthony Adame, Franz Marxreiter, Brit Mollenhauer, Douglas Galasko, Edit Irén Buzás, Ursula Schlötzer-Schrehardt, Katrin Marcus, Wei Xiang, Dieter Chichung Lie, Kostas Vekrellis, Eliezer Masliah, Jürgen Winkler, Jochen Klucken
The autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies, including Parkinson disease and dementia with Lewy bodies (DLB). Emerging evidence suggests that ALP influences SNCA release, but the underlying cellular mechanisms are not well understood. Several studies identified SNCA in exosome/extracellular vesicle (EV) fractions. EVs are generated in the multivesicular body compartment and either released upon its fusion with the plasma membrane, or cleared via the ALP...
December 4, 2017: Autophagy
https://www.readbyqxmd.com/read/29193463/placental-exosomes-a-proxy-to-understand-pregnancy-complications
#5
Jin Jin, Ramkumar Menon
Exosomes (30- to 150-nm particles), originating from multivesicular bodies by the invagination of the endosomal membrane, are communication channels between cells. Exosomes are released by various cell types and cargo proteins, lipids, and nucleic acids reflecting the physiologic status of their cells of origin and cause functional changes in recipient cells, which are likely dependent on their quantity and/or cargo contents. Recently, placental exosomes, produced by various placental cell types, have been isolated from maternal blood using the placental protein-specific marker, placental alkaline phosphatase (PLAP)...
November 28, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29192023/g%C3%AE-s-protein-binds-ubiquitin-to-regulate-epidermal-growth-factor-receptor-endosomal-sorting
#6
Xuezhi Li, Danny Létourneau, Brian Holleran, Richard Leduc, Pierre Lavigne, Christine Lavoie
The Gαs subunit is classically involved in the signal transduction of G protein-coupled receptors (GPCRs) at the plasma membrane. Recent evidence has revealed noncanonical roles for Gαs in endosomal sorting of receptors to lysosomes. However, the mechanism of action of Gαs in this sorting step is still poorly characterized. Here, we report that Gαs interacts with ubiquitin to regulate the endosomal sorting of receptors for lysosomal degradation. We reveal that the N-terminal extremity of Gαs contains a ubiquitin-interacting motif (UIM), a sorting element usually found in the endosomal sorting complex required for transport (ESCRT) machinery responsible for sorting ubiquitinated receptors into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs)...
November 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29184027/arabidopsis-vps38-is-required-for-vacuolar-trafficking-but-dispensable-for-autophagy
#7
Han Nim Lee, Xavier Zarza, Jeong Hun Kim, Min Ji Yoon, Sang-Hoon Kim, Jae-Hoon Lee, Nadine Paris, Teun Munnik, Marisa S Otegui, Taijoon Chung
Phosphatidylinositol 3-phosphate (PI3P) is a signaling molecule that controls a variety of processes in endosomal, autophagic and vacuolar/lysosomal trafficking in yeasts and mammals. Vacuolar protein sorting 34 (Vps34) is a conserved phosphatidylinositol 3-kinase (PI3K) present in multiple complexes with specific functions and regulation. In yeast, the PI3K complex II, consisting of Vps34p, Vps15p, Vps30p/Atg6p, and Vps38p, is essential for vacuolar protein sorting. Here, we describe the Arabidopsis thaliana homolog of yeast Vps38p and human UV radiation resistance-associated gene (UVRAG) protein...
November 28, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29142103/an-intracellular-activation-of-smoothened-independent-of-hedgehog-stimulation-in-drosophila
#8
Kai Jiang, Yajuan Liu, Jie Zhang, Jianhang Jia
Smoothened (Smo), a GPCR family protein, plays a critical role in the reception and transduction of Hedgehog (Hh) signal. Smo is phosphorylated and activated on the cell surface, however, it is unknown whether Smo can be intracellularly activated. Here, we demonstrate that inactivation of the ESCRT-III causes dramatic accumulation of Smo, and subsequent activation of Hh signaling. In contrast, inactivation of ESCRTs 0-II induces mild Smo accumulation. We provide evidence that Kurtz (Krz), the Drosophila β-arrestin2, acts in parallel with the ESCRTs 0-II pathway to sort Smo to the multivesicular bodies and lysosome-mediated degradation...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29140158/endosomal-trafficking-regulates-receptor-mediated-transcytosis-of-antibodies-across-the-blood-brain-barrier
#9
Arsalan S Haqqani, Christie E Delaney, Eric Brunette, Ewa Baumann, Graham K Farrington, William Sisk, John Eldredge, Wen Ding, Tammy-Lynn Tremblay, Danica B Stanimirovic
Current methods for examining antibody trafficking are either non-quantitative such as immunocytochemistry or require antibody labeling with tracers. We have developed a multiplexed quantitative method for antibody 'tracking' in endosomal compartments of brain endothelial cells. Rat brain endothelial cells were co-incubated with blood-brain barrier (BBB)-crossing FC5, monovalent FC5Fc or bivalent FC5Fc fusion antibodies and control antibodies. Endosomes were separated using sucrose-density gradient ultracentrifugation and analyzed using multiplexed mass spectrometry to simultaneously quantify endosomal markers, receptor-mediated transcytosis (RMT) receptors and the co-incubated antibodies in each fraction...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29135058/distinct-features-of-multivesicular-body-lysosome-fusion-revealed-by-a-new-cell-free-content-mixing-assay
#10
Mahmoud Abdul Karim, Dieter Ronny Samyn, Sevan Mattie, Christopher Leonard Brett
When marked for degradation, surface receptor and transporter proteins are internalized and delivered to endosomes where they are packaged into intralumenal vesicles (ILVs). Many rounds of ILV formation create multivesicular bodies (MVBs) that fuse with lysosomes exposing ILVs to hydrolases for catabolism. Despite being critical for protein degradation, the molecular underpinnings of MVB-lysosome fusion remain unclear, although machinery underlying other lysosome fusion events is implicated. But how then is specificity conferred? And how is MVB maturation and fusion coordinated for efficient protein degradation? To address these questions, we developed a cell-free MVB-lysosome fusion assay using S...
November 14, 2017: Traffic
https://www.readbyqxmd.com/read/29133526/involvement-of-g%C3%AE-%C3%AE-subunits-of-gi-protein-coupled-with-s1p-receptor-on-multivesicular-endosomes-in-f-actin-formation-and-cargo-sorting-into-exosomes
#11
Taketoshi Kajimoto, Nesma Nabil Ibrahim Mohamed, Shaymaa Mohamed Mohamed Badawy, Shubi Ambwene Matovelo, Mitsuhiro Hirase, Shunsuke Nakamura, Daisuke Yoshida, Taro Okada, Takeshi Ijuin, Shun-Ichi Nakamura
Exosomes play a critical role in cell-to-cell communication by delivering cargo molecules to recipient cells. However, the mechanism underlying the generation of the exosomal multivesicular endosome (MVE) is one of the mysteries in the field of endosome research. Although sphingolipid metabolites such as ceramide and sphingosine 1-phosphate (S1P) are known to play important roles in MVE formation and maturation, the detailed molecular mechanisms are still unclear. Here, we show that Rho family GTPases, including Cdc42 and Rac1, are constitutively activated on exosomal MVEs and are regulated by S1P signaling as measured by fluorescence resonance energy transfer (FRET)-based conformational changes...
November 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29129923/ist1-regulates-escrt-iii-assembly-and-function-during-multivesicular-endosome-biogenesis-in-caenorhabditis-elegans-embryos
#12
E B Frankel, Raakhee Shankar, James J Moresco, John R Yates, Niels Volkmann, Anjon Audhya
Degradation of most integral membrane proteins is directed by the endosomal sorting complex required for transport (ESCRT) machinery, which selectively targets ubiquitin-modified cargoes into intralumenal vesicles (ILVs) within multivesicular endosomes (MVEs). To better understand the mechanisms underlying ESCRT-mediated formation of ILVs, we exploited the rapid, de novo biogenesis of MVEs during the oocyte-to-embryo transition in C. elegans. In contrast to previous models suggesting that ILVs form individually, we demonstrate that they remain tethered to one another subsequent to internalization, arguing that they bud continuously from stable subdomains...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29107112/the-emerging-role-of-exosome-derived-non-coding-rnas-in-cancer-biology
#13
Qing Fan, Liang Yang, Xiaodong Zhang, Xueqiang Peng, Shibo Wei, Dongming Su, Zhenhua Zhai, Xiangdong Hua, Hangyu Li
Exosomes are a new means of intercellular information exchange that have aroused great research interest. Long neglected in research, exosomes were deemed nonfunctional cellular components to be discarded. However, it has been gradually revealed that exosomes are an important tool for the exchange of intercellular information and material. Exosomes contain specific repertoires of non-coding RNAs (ncRNAs, including microRNA and lncRNA), indicating that a specific RNA sorting mechanism may exist. Correspondingly, intracellular multivesicular bodies (MVBs) are produced after fusion with the cell membrane to release exosomes rather than inducing autophagy, which reveals that there may be a specific regulatory mechanism for MVB secretion...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29101310/snare-phosphorylation-a-control-mechanism-for-insulin-stimulated-glucose-transport-and-other-regulated-exocytic-events
#14
REVIEW
Kamilla M E Laidlaw, Rachel Livingstone, Mohammed Al-Tobi, Nia J Bryant, Gwyn W Gould
Trafficking within eukaryotic cells is a complex and highly regulated process; events such as recycling of plasma membrane receptors, formation of multivesicular bodies, regulated release of hormones and delivery of proteins to membranes all require directionality and specificity. The underpinning processes, including cargo selection, membrane fusion, trafficking flow and timing, are controlled by a variety of molecular mechanisms and engage multiple families of lipids and proteins. Here, we will focus on control of trafficking processes via the action of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family of proteins, in particular their regulation by phosphorylation...
November 3, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29081510/isolation-and-characterization-of-urinary-extracellular-vesicles-implications-for-biomarker-discovery
#15
REVIEW
Michael L Merchant, Ilse M Rood, Jeroen K J Deegens, Jon B Klein
Urine is a valuable diagnostic medium and, with the discovery of urinary extracellular vesicles, is viewed as a dynamic bioactive fluid. Extracellular vesicles are lipid-enclosed structures that can be classified into three categories: exosomes, microvesicles (or ectosomes) and apoptotic bodies. This classification is based on the mechanisms by which membrane vesicles are formed: fusion of multivesicular bodies with the plasma membranes (exosomes), budding of vesicles directly from the plasma membrane (microvesicles) or those shed from dying cells (apoptotic bodies)...
December 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29080983/autoimmune-responses-to-exosomes-and-candidate-antigens-contribute-to-type-1-diabetes-in-non-obese-diabetic-mice
#16
REVIEW
Yang D Dai, Huiming Sheng, Peter Dias, M Jubayer Rahman, Roman Bashratyan, Danielle Regn, Kristi Marquardt
PURPOSE OF REVIEW: The initial autoimmune trigger of type 1 diabetes (T1D) remains unclear. In non-obese diabetic (NOD) mice, islet inflammation starts early in life, suggesting the presence of an endogenous trigger for the spontaneous autoimmune response in this T1D mouse model. In this review, we argue that abnormal release of exosomes might be the trigger of the early inflammatory and autoimmune responses in the islets. RECENT FINDINGS: Exosomes are nano-sized membrane complexes that are secreted by cells following fusion of late endosomes and/or multivesicular bodies with the plasma membrane...
October 28, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/29074498/ferritin-is-secreted-via-two-distinct-non-classical-vesicular-pathways
#17
Marianna Truman-Rosentsvit, Dina Berenbaum, Lior Spektor, Lyora A Cohen, Shirly Belizowsky-Moshe, Lena Lifshitz, Jing Ma, Wei Li, Ellina Kesselman, Inbal Abutbul-Ionita, Dganit Danino, Lucia Gutierrez, Huihui Li, Kuanyu Li, Huifang Lou, Maria Regoni, Maura Poli, Fabian Glaser, Tracey A Rouault, Esther G Meyron-Holtz
Ferritin turnover plays a major role in tissue iron homeostasis and ferritin misfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a non-toxic and bio-available form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical ER-Golgi secretion but is found in serum and is secreted via a non-classical lysosomal secretion pathway...
October 26, 2017: Blood
https://www.readbyqxmd.com/read/29062835/toward-exosome-based-therapeutics-isolation-heterogeneity-and-fit-for-purpose-potency
#18
Gareth R Willis, Stella Kourembanas, S Alex Mitsialis
Exosomes are defined as submicron (30-150 nm), lipid bilayer-enclosed extracellular vesicles (EVs), specifically generated by the late endosomal compartment through fusion of multivesicular bodies with the plasma membrane. Produced by almost all cells, exosomes were originally considered to represent just a mechanism for jettisoning unwanted cellular moieties. Although this may be a major function in most cells, evolution has recruited the endosomal membrane-sorting pathway to duties beyond mere garbage disposal, one of the most notable examples being its cooption by retroviruses for the generation of Trojan virions...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29051571/a-new-cellular-type-in-invertebrates-first-evidence-of-telocytes-in-leech-hirudo-medicinalis
#19
Laura Pulze, Nicolò Baranzini, Rossana Girardello, Annalisa Grimaldi, Lidia Ibba-Manneschi, Enzo Ottaviani, Marcella Reguzzoni, Gianluca Tettamanti, Magda de Eguileor
Telocytes, a peculiar cell type, were recently found in vertebrates. Hence this cell system has been reported as ubiquitous in the bodies of mammals and interpreted as an important player in innate immunity and tissue regeneration, it is reasonable to look for it also in invertebrates, that rely their integrity solely by innate immunity. Here we describe, at morphological and functional level, invertebrate telocytes from the body of leech Hirudo medicinalis (Annelida), suggesting how these cells, forming a resident stromal 3D network, can influence or participate in different events...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29050192/-advances-in-research-of-exosomes-and-age-related-macular-degeneration
#20
M Q Xu, X D Sun
Exosomes are small vesicles with a molecular diameter of 30 to 100 nm, which are secreted into the cell after the fusion of the multivesicular bodies with the plasma membrane. Exosomes contain various molecular constituents of their cell origin, including proteins, microRNAs and lipids. Different cell-derived exosomes have different biological functions. Exosomes play a very important role in the development and progression of age-related macular degeneration (AMD). The exosomes derived from the eye are involved in the processes of cell growth, metastasis, angiogenesis and immunosuppression by transferring contents to adjacent or distant cells...
October 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
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