Stochastic Modeling of Nanoparticle Internalization and Expulsion Through Receptor-Mediated Transcytosis
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Characterization of Efferosome Maturation and the Processing of Apoptotic Bodies
Western University Scholarship@Western Electronic Thesis and Dissertation Repository 8-15-2014 12:00 AM Characterization of Efferosome Maturation and the Processing of Apoptotic Bodies Yohan Kim The University of Western Ontario Supervisor Dr. Bryan Heit The University of Western Ontario Graduate Program in Microbiology and Immunology A thesis submitted in partial fulfillment of the equirr ements for the degree in Master of Science © Yohan Kim 2014 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Cell Biology Commons, Immunity Commons, and the Other Immunology and Infectious Disease Commons Recommended Citation Kim, Yohan, "Characterization of Efferosome Maturation and the Processing of Apoptotic Bodies" (2014). Electronic Thesis and Dissertation Repository. 2268. https://ir.lib.uwo.ca/etd/2268 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. CHARACTERIZATION OF EFFEROSOME MATURATION AND THE PROCESSING OF APOPTOTIC BODIES (Thesis format: Monologue) by Yohan Kim Graduate Program in Microbiology and Immunology A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science The School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada © Yohan Kim 2014 Abstract Every day billions of cells in our bodies undergo apoptosis and are cleared through efferocytosis – a phagocytosis-like process in which phagocytes engulf and degrade apoptotic cells. Proper processing of efferosomes prevents inflammation and immunogenic presentation of antigens. -
Transcytosis of Ngcam in Epithelial Cells Reflects Differential Signal
Published August 8, 2005 JCB: ARTICLE Transcytosis of NgCAM in epithelial cells reflects differential signal recognition on the endocytic and secretory pathways Eric Anderson, Sandra Maday, Jeff Sfakianos, Michael Hull, Bettina Winckler, David Sheff, Heike Fölsch, and Ira Mellman Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06520 gCAM is a cell adhesion molecule that is largely ability to interact with clathrin adaptors. Based on the be- axonal in neurons and apical in epithelia. In Ma- havior of various NgCAM mutants, it appears that after Ndin-Darby canine kidney cells, NgCAM is tar- arrival at the basolateral surface, the AP-1B interaction geted to the apical surface by transcytosis, being first in- site is silenced by phosphorylation of Tyr33. This slows en- serted into the basolateral domain from which it is docytosis and inhibits basolateral recycling from endo- internalized and transported to the apical domain. Initial somes, resulting in NgCAM transcytosis due to a cryptic basolateral transport is mediated by a sequence motif apical targeting signal in its extracellular domain. Thus, Downloaded from (Y33RSL) decoded by the AP-1B clathrin adaptor complex. transcytosis of NgCAM and perhaps other membrane This motif is a substrate in vitro for tyrosine phosphoryla- proteins may reflect the spatial regulation of recognition tion by p60src, a modification that disrupts NgCAM’s by adaptors such as AP-1B. on March 10, 2017 Introduction The generation and maintenance of cellular polarity is an es- ously resorted in endosomes to maintain their polarized distri- sential aspect of multicellular life. -
Apical-To-Basolateral Transcytosis of Photoreceptor Outer Segments Induced by Lipid Peroxidation Products in Human Retinal Pigment Epithelial Cells
Retinal Cell Biology Apical-to-Basolateral Transcytosis of Photoreceptor Outer Segments Induced by Lipid Peroxidation Products in Human Retinal Pigment Epithelial Cells Tim U. Krohne,1 Frank G. Holz,1 and Ju¨rgen Kopitz2 PURPOSE. Progressive accumulation of extracellular material at posit formation and drusen biogenesis in AMD. (Invest Oph- the basolateral side of the retinal pigment epithelium (RPE) is thalmol Vis Sci. 2010;51:553–560) DOI:10.1167/iovs.09-3755 a key event in the pathogenesis of age-related macular degen- eration (AMD). The authors previously demonstrated that mod- rogressive deposition of extracellular material between the ifications with lipid peroxidation products, such as 4-hy- basolateral side of the retinal pigment epithelium (RPE) droxynonenal (HNE) and malondialdehyde (MDA), stabilize P and adjacent Bruch’s membrane is a hallmark of early-stage photoreceptor outer segment (POS) proteins against lysosomal age-related macular degeneration (AMD).1,2 Among the various degradation. Herein, they tested RPE cells for the basolateral histologically and clinically distinguishable manifestations of release of undegraded modified POS proteins. sub-RPE deposits, basal linear deposits (BLinD) and soft drusen METHODS. Polarized cultures of the human RPE cell line are recognized as specific for AMD.3,4 Both BLinD and soft ARPE-19 on permeable membranes were incubated with io- drusen represent accumulations of material described as mem- dine-125–labeled POS on the apical side. After 24 hours, radio- branous debris5 between the RPE basement membrane and the activity was quantified in apical medium, cell lysates, and inner collagenous layer of Bruch’s membrane and are, there- basolateral medium after separation of undegraded proteins by fore, considered diffuse and focal manifestations, respectively, precipitation. -
Thyroid Hormone Synthesis Continues Despite Biallelic Thyroglobulin Mutation with Cell Death
Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death Xiaohan Zhang, … , Viviana A. Balbi, Peter Arvan JCI Insight. 2021. https://doi.org/10.1172/jci.insight.148496. Research In-Press Preview Endocrinology Graphical abstract Find the latest version: https://jci.me/148496/pdf Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death Authors: Xiaohan Zhang1, Aaron P. Kellogg1, Cintia E. Citterio1,2,3, Hao Zhang1, Dennis Larkin1, Yoshiaki Morishita1,4, Héctor M. Targovnik2,3, Viviana Balbi5, and Peter Arvan1* Affiliations: 1Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, MI 48105 2Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética/Cátedra de Genética. Buenos Aires, Argentina. 3CONICET, Universidad de Buenos Aires, Instituto de Inmunología, Genética y Metabolismo (INIGEM), Buenos Aires, Argentina 4Division of Diabetes, Department of Internal Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan 5Department of Endocrinology and Growth, Hospital de Niños Sor María Ludovica, La Plata, Argentina Conflict of interest: The authors declare that no conflict of interest exists. Short Title: Thyroxine synthesis from dead cells 1 Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from bi-allelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. -
Membrane Transport Quiz
Membrane Transport Quiz 1. Which of the following is an example of extracellular fluid? a. Cytosol b. Plasma c. Interstitial Fluid d. Both b and c 2. Which of the following correctly describes passive transport? a. the cell uses ATP in passive transport b. most pumps are examples of passive transport c. diffusion is an example of passive transport d. exocytosis is an example of passive transport 3. Simple diffusion occurs ______________. a. with transporters in the cell membrane b. directly across the cell membrane c. through exocytosis d. through endocytosis 4. Which of the following is an example of active transport? a. Filtration b. Osmosis c. Endocytosis d. Exocytosis e. Both c and d 5. Which type of active transport uses ATP directly? a. Primary Active Transport b. Secondary Active Transport c. Both a and b 6. Which of the following is an example of receptor mediated endocytosis? a. Phagocytosis b. Primary Active Transport c. Exocytosis d. ALL are For use with TCC iTunes University Membrane Transport Lecture. 1 Developed by: Martha Kutter 2009 for the Learning Commons at Tallahassee Community College. 7. A transporter that moves one type of particle in one direction is _______________. a. Uniporter b. Symporter c. Antiporter 8. A transporter the moves two different particles in two different directions is ________. a. Endocytosis b. Exocytosis c. Uniporter d. Symporter e. Antiporter 9. Which of the following is an example of a primary active transporter? a. Na+/Ca2+ transporter on cardiac contractile cells b. Na+ channels on neurons c. Na+/K+ ATPase on all cells d. -
Transcytosis of Trka Leads to Diversification of Dendritic Signaling
www.nature.com/scientificreports OPEN Transcytosis of TrkA leads to diversifcation of dendritic signaling endosomes Received: 8 January 2018 Kelly Barford 1, Austin Keeler2, Lloyd McMahon1, Kathryn McDaniel1, Chan Choo Yap1, Accepted: 5 March 2018 Christopher D. Deppmann2,3 & Bettina Winckler1 Published: xx xx xxxx The development of the peripheral nervous system relies on long-distance signaling from target organs back to the soma. In sympathetic neurons, this long-distance signaling is mediated by target derived Nerve Growth Factor (NGF) interacting with its axonal receptor, TrkA. This ligand receptor complex internalizes into what is commonly referred to as the signaling endosome which is transported retrogradely to the soma and dendrites to mediate survival signaling and synapse formation, respectively. The molecular identity of signaling endosomes in dendrites has not yet been determined. Here, we perform a detailed analysis of TrkA endosomal compartments and trafcking patterns. We fnd that signaling endosomes are not uniform but molecularly diversifed into Rab7 (late endosome) and Rab11 (recycling endosome) populations in axons and dendrites in vitro and in the soma in vivo. Surprisingly, TrkA-NGF signaling endosomes in dendrites undergo dynamic trafcking events, including putative fusion and fssion. Overall, we fnd that signaling endosomes do not remain as a singular endosomal subtype but instead exist in multiple populations that undergo dynamic endosomal trafcking events. These dynamic events might drive functional diversifcation of the signaling endosome. Te development of the sympathetic and sensory nervous systems requires the target derived neurotrophic factor, Nerve Growth Factor (NGF)1. Te molecular and cellular mechanisms that enable target derived NGF to transmit signals long distances from distal axons to the cell body have been under intense investigation for several years. -
Exo-Endocytosis at Mossy Fiber Terminals: Toward Capacitance Measurements in Cells with Arbitrary Geometry
Exo-endocytosis at mossy fiber terminals: Toward capacitance measurements in cells with arbitrary geometry Christopher Kushmerick and Henrique von Gersdorff* The Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239 xocytosis and endocytosis are real time as a decrease in membrane ments have been made on secretory ubiquitous cellular phenomena capacitance back to baseline resting lev- cells for which the compact isopotential necessary for diverse functions els (6–9). approximation seems, prima facie,tobe such as secretion, internal sig- Most measurements obtained to date justified, including adrenal chromaffin Enaling, protein traffic, and motility. have relied on one of two general tech- cells (10), mast cells (11), and neuroen- Many different techniques have been niques to relate membrane current to docrine cells (12), which secrete via developed to assay exocytosis and endo- capacitance (6, 9). Time-domain meth- large dense-core vesicles. In addition, cytosis, but to date only electrical mea- ods use the amplitude and time course small clear-core synaptic vesicle fusion surements of plasma membrane capaci- of membrane current relaxations after and membrane retrieval have been mea- tance have had the time resolution step changes in electrical potential to sured from retinal bipolar cell terminals necessary to capture both the fusion and determine cell membrane parameters. (2, 3, 13), hair cells (4, 5), and photore- reuptake of small clear-core vesicle ceptors (14). However, these sensory membrane during fast neurotransmis- neurons contain nonconventional rib- sion. In this issue of PNAS, Hallermann bon-type active zones (3, 13, 15). et al. (1) present capacitance measure- These are the first Recently, attempts have been made to ments from hippocampal mossy fiber measure exocytosis in cells with complex nerve terminals during stimulated exocy- membrane capacitance geometry and multiple electrical com- tosis. -
A New Look at Transudation: the Apocrine Connection
Physiol. Res. 69: 227-244, 2020 https://doi.org/10.33549/physiolres.934229 REVIEW A New Look at Transudation: The Apocrine Connection Robert FARKAŠ1, Milan BEŇO1, Denisa BEŇOVÁ-LISZEKOVÁ1, Ivan RAŠKA2, Otakar RAŠKA2,3 1Laboratory of Developmental Genetics, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic, 2Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic, 3Institute of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic Received June 9, 2019 Accepted December 20, 2019 Epub Ahead of Print March 23, 2020 Summary Corresponding authors Transcellular trafficking in which various molecules are Robert Farkaš, Laboratory of Developmental Genetics, Institute transported across the interior of a cell, is commonly classified as of Experimental Endocrinology, Biomedical Research Center, transcytosis. However, historically this term has been used Slovak Academy of Sciences, Dúbravská cesta 9, 84505 synonymously with transudation. In both cases transcellular Bratislava, Slovak Republic. E-mail: [email protected]. Otakar trafficking starts with the internalization of proteins or other Raška, Third Faculty of Medicine, Charles University, Ruská 87, compounds on the basal or basolateral side of a cell and 10000 Prague, Czech Republic. E-mail: [email protected] continues by their transport across the interior to the apical pole (or vice versa) where they are subsequently released. -
Exocytosis by Networks of Rab Gtpases Decoding the Regulation
The Journal of Immunology Decoding the Regulation of Mast Cell Exocytosis by Networks of Rab GTPases Nurit P. Azouz,* Takahide Matsui,† Mitsunori Fukuda,† and Ronit Sagi-Eisenberg* Exocytosis is a key event in mast cell functions. By this process, mast cells release inflammatory mediators, contained in secretory granules (SGs), which play important roles in immunity and wound healing but also provoke allergic and inflammatory responses. The mechanisms underlying mast cell exocytosis remained poorly understood. An essential step toward deciphering the mechanisms behind exocytosis is the identification of the cellular components that regulate this process. Because Rab GTPases regulate specific trafficking pathways, we screened 44 Rabs for their functional impacts on exocytosis triggered by the Fc«RI or combination of Ca2+ ionophore and phorbol ester. Because exocytosis involves the continuous reorganization of the actin cytoskeleton, we also repeated our screen in the presence of cytochalasin D that inhibits actin polymerization. In this paper, we report on the identification of 30 Rabs as regulators of mast cell exocytosis, the involvement of 26 of which has heretofore not been recognized. Unexpectedly, these Rabs regulated exocytosis in a stimulus-dependent fashion, unless the actin skeleton was disrupted. Functional clustering of the identified Rabs suggested their classification as Rabs involved in SGs biogenesis or Rabs that control late steps of exocytosis. The latter could be further divided into Rabs that localize to the SGs and Rabs that regulate transport from the endocytic recycling compartment. Taken together, these findings unveil the Rab networks that control mast cell exocytosis and provide novel insights into their mechanisms of action. -
Epithelial Cells Inhibit HIV-1 Transcytosis Across Human HIV-1
Mucosal and Plasma IgA from HIV-1-Exposed Uninfected Individuals Inhibit HIV-1 Transcytosis Across Human Epithelial Cells This information is current as of September 30, 2021. Claudia Devito, Kristina Broliden, Rupert Kaul, Lennart Svensson, Kari Johansen, Peter Kiama, Joshua Kimani, Lucia Lopalco, Stefania Piconi, Job J. Bwayo, Francis Plummer, Mario Clerici and Jorma Hinkula J Immunol 2000; 165:5170-5176; ; Downloaded from doi: 10.4049/jimmunol.165.9.5170 http://www.jimmunol.org/content/165/9/5170 http://www.jimmunol.org/ References This article cites 39 articles, 10 of which you can access for free at: http://www.jimmunol.org/content/165/9/5170.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 30, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Mucosal and Plasma IgA from HIV-1-Exposed Uninfected Individuals Inhibit HIV-1 Transcytosis Across Human Epithelial Cells1 Claudia Devito,* Kristina Broliden,2* Rupert Kaul,† Lennart Svensson,‡ Kari Johansen,‡ Peter Kiama,† Joshua Kimani,† Lucia Lopalco,§ Stefania Piconi,¶ Job J. -
Exocytosis and Endocytosis
Exocytosis and Endocytosis Exocytosis and Endocytosis A Closer Look at Cell Membranes . Aim: How do large particles enter and exit cells? . Do Now: Name some molecules/materials that enter and exit the cell. How would you describe the cell membrane that allows passage of these materials? Exocytosis and Endocytosis Exocytosis and Endocytosis . Exocytosis (out of the cell) • The fusion of a vesicle with the cell membrane, releasing its contents to the surroundings . Endocytosis (into the cell) • The formation of a vesicle from cell membrane, enclosing materials near the cell surface and bringing them into the cell Exocytosis and Endocytosis Endocytosis . Phagocytosis – solid . Pinocytosis – liquid (general) Endocytosis: . Uptake of substances . Transport of protein or lipid components of compartments . Metabolic or division signaling . Defense to microorganisms Endocytosis . Clathrin-coated vesicles . Non-clathrin coated vesicles . Macropinocytosis . Potocytosis Exocytosis and Endocytosis Endocytosis Required: . signal . membrane receptor (Fc receptor for Ab) . formation of pseudopodium . cortical actin network The formed vesicle: phagosome (hetero-; auto-) Endocytosis . Clathrin-coated vesicles . Non-clathrin coated vesicles . Macropinocytosis . Potocytosis Endocytosis and Exocytosis Examples Three Pathways of Endocytosis . Bulk-phase endocytosis • Extracellular fluid is captured in a vesicle and brought into the cell; the reverse of exocytosis . Receptor-mediated endocytosis • Specific molecules bind to surface receptors, which are then enclosed in an endocytic vesicle . Phagocytosis • Pseudopods engulf target particle and merge as a vesicle, which fuses with a lysosome in the cell Phagocytosis (“engulfment”) Exocytosis and Endocytosis Membrane Cycling . Exocytosis and endocytosis continually replace and withdraw patches of the plasma membrane . New membrane proteins and lipids are made in the ER, modified in Golgi bodies, and form vesicles that fuse with plasma membrane Exocytic Vesicle 5.5 Key Concepts: Membrane Trafficking . -
Lysosomal Biology and Function: Modern View of Cellular Debris Bin
cells Review Lysosomal Biology and Function: Modern View of Cellular Debris Bin Purvi C. Trivedi 1,2, Jordan J. Bartlett 1,2 and Thomas Pulinilkunnil 1,2,* 1 Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS B3H 4H7, Canada; [email protected] (P.C.T.); jjeff[email protected] (J.J.B.) 2 Dalhousie Medicine New Brunswick, Saint John, NB E2L 4L5, Canada * Correspondence: [email protected]; Tel.: +1-(506)-636-6973 Received: 21 January 2020; Accepted: 29 April 2020; Published: 4 May 2020 Abstract: Lysosomes are the main proteolytic compartments of mammalian cells comprising of a battery of hydrolases. Lysosomes dispose and recycle extracellular or intracellular macromolecules by fusing with endosomes or autophagosomes through specific waste clearance processes such as chaperone-mediated autophagy or microautophagy. The proteolytic end product is transported out of lysosomes via transporters or vesicular membrane trafficking. Recent studies have demonstrated lysosomes as a signaling node which sense, adapt and respond to changes in substrate metabolism to maintain cellular function. Lysosomal dysfunction not only influence pathways mediating membrane trafficking that culminate in the lysosome but also govern metabolic and signaling processes regulating protein sorting and targeting. In this review, we describe the current knowledge of lysosome in influencing sorting and nutrient signaling. We further present a mechanistic overview of intra-lysosomal processes, along with extra-lysosomal processes, governing lysosomal fusion and fission, exocytosis, positioning and membrane contact site formation. This review compiles existing knowledge in the field of lysosomal biology by describing various lysosomal events necessary to maintain cellular homeostasis facilitating development of therapies maintaining lysosomal function.