DOCSLIB.ORG

The Role of the Exocyst in Exocytosis and Cell Migration

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of the Exocyst in Exocytosis and Cell Migration University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Summer 2010 The Role of the Exocyst in Exocytosis and Cell Migration Jianglan Liu University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Cell Biology Commons Recommended Citation Liu, Jianglan, "The Role of the Exocyst in Exocytosis and Cell Migration" (2010). Publicly Accessible Penn Dissertations. 201. https://repository.upenn.edu/edissertations/201 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/201 For more information, please contact [email protected]. The Role of the Exocyst in Exocytosis and Cell Migration Abstract The exocyst, an evolutionarily conserved octameric protein complex, plays a crucial role in the tethering of post-Golgi secretory vesicles to the plasma membrane for exocytosis and cell migration. How the exocyst is targeted to sites of exocytosis and how this complex regulates cell migration are poorly understood. I have carried out experiments to characterize Exo70, a component of the exocyst complex. Firstly, I found that Exo70 directly interacts with phosphatidylinositol 4,5-bisphosphate through positively charged residues at its C-terminus, and this interaction is critical for the plasma membrane targeting of Exo70. Using the ts045 vesicular stomatitis virus glycoprotein trafficking assay, I found that the Exo70-lipid interaction is critical for the docking and fusion of post-Golgi secretory vesicles with the plasma membrane. Secondly, I demonstrate that the exocyst plays a pivotal role in tumor cell invasion. Invadopodia are actin-rich membrane protrusions formed by tumor cells that degrade the extracellular matrix for invasion. Depletion of the exocyst component Exo70 or Sec8 led to failure in invadopodia formation in MDA-MB-231 cells expressing constitutively active c-Src, whereas the overexpression of Exo70 promoted invadopodia formation. Disrupting the exocyst function by RNA interference of EXO70 or SEC8, or by expression of a dominant negative fragment of Exo70 blocked the secretion of matrix metalloproteinases. I further found that the exocyst interacts with the Arp2/3 complex in cells with high invasion potential; blocking the exocyst-Arp2/3 interaction inhibited Arp2/3-mediated actin polymerization and invadopodia formation. Finally, the exocyst also functions in directly regulating Arp2/ 3-mediated actin polymerization. Using pyrene actin assay and total internal reflection fluorescence microscopy, I found that Exo70 synergizes with WAVE2 to promote Arp2/3-mediated actin polymerization and branching. In addition, I have examined how the Exo70-Arp2/3 interaction is regulated in the cell downstream of growth factor signaling. Overall, these studies provide mechanistic insights to the function of the exocyst in exocytosis and cell migration. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Biology First Advisor Wei Guo Keywords Exocytosis, Exocyst, Invadopodia, The Arp2/3 complex, cell migration, actin polymerization Subject Categories Cell Biology This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/201 THE ROLE OF THE EXOCYST IN EXOCYTOSIS AND CELL MIGRATION JIANGLAN LIU A DISSERTATION in BIOLOGY Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2010 Supervisor of Dissertation _________________________________ Wei Guo, Associate Professor of Biology Graduate Group Chairperson _________________________________ Paul Sniegowski, Associate Professor of Biology Dissertation Committee Tatyana Svitkina, Associate Professor of Biology Michael Lampson, Assistant Professor of Biology Kimberly Gallagher, Assistant Professor of Biology Margaret Chou, Associate Professor of Pathology and Laboratory Medicine Mickey Marks, Associate Professor of Pathology and Laboratory Medicine ACKNOWLEDGEMENTS First of all, I would like to give my deepest gratitude to my mentor Dr. Wei Guo. I regard Wei as my scientific father as he guided me into the wonderful scientific field and directed me all the way till now. I am so impressed with his enthusiasms and curiosity on science, his persistence on research and his extensive knowledge. And I really appreciate that he gives me inspiring advices and warm encouragements in all the time of research. I would benefit from his mentoring throughout my entire scientific career. Secondly, I really appreciate all the members in my thesis committee: Prof. Tatyana Svitkina, Prof. Margaret M. Chou, Prof. Mickey Marks, Prof. Kimberly Gallagher and Prof. Michael A.Lampson. They have committed much time and efforts to follow my research and have always been a great source of constructive suggestions and encouragements. I enjoy the wonderful time that I have spent with all the previous and current members of Guo lab. They make the lab such a pleasant place for everyday work. They are not only my scientific partners, but also my incredible friends. In particular, I would like to thank Dr. Bing He who has offered me so much help and valuable advices. I appreciate Dr. Xiaofeng Zuo for his contribution to the first part of this study. I am grateful to Dr Xiaoyu Zhang and Jian Zhang for their nice help since I ii entered the lab. I also want to thank Dr. Kelly Orlando for her help on my scientific English writing. Finally, I want to thank all other lab folks for their constant discussions and encouragements. I would also like to extend thanks to the people who have been instrumental in completion of this work. I am grateful to Prof. Susette C. Mueller, Dr. Vira V. Artym and Mr. Peter Johnson for their collaboration on the invadopodia research; Prof. Yale Goldman and Dr. Yujie Sun for their collaboration on the TIRFM experiments; Dr. Jian Jing for giving me advices for zymography experiments; Prof. Roberto Dominguez, Dr. Grzegorz Rebowski and Dr. Boczkowska Malgorzata for their help on the pyrene actin assay. Finally, I would like to give my special thanks to my family. I want to thank my parents with my heart for their love, support and encouragement throughout my life. Most of all, I would give my thanks to my dear husband, Peng Yue. He is my labmate, my soulmate and my lifemate. His solid help for my research and his endless love for my life make me strong enough to go this far. I want to give my last but most special thanks to my little angel Shannon Xianning Yue. You make mommy’s life complete. Love you forever. iii ABSTRACT THE ROLE OF THE EXOCYST IN EXOCYTOSIS AND CELL MIGRATION Jianglan Liu Supervisor: Dr. Wei Guo The exocyst, an evolutionarily conserved octameric protein complex, plays a crucial role in the tethering of post-Golgi secretory vesicles to the plasma membrane for exocytosis and cell migration. How the exocyst is targeted to sites of exocytosis and how this complex regulates cell migration are poorly understood. I have carried out experiments to characterize Exo70, a component of the exocyst complex. Firstly, I found that Exo70 directly interacts with phosphatidylinositol 4,5-bisphosphate through positively charged residues at its C-terminus, and this interaction is critical for the plasma membrane targeting of Exo70. Using the ts045 vesicular stomatitis virus glycoprotein trafficking assay, I found that the Exo70-lipid interaction is critical for the docking and fusion of post-Golgi secretory vesicles with the plasma membrane. Secondly, I demonstrate that the exocyst plays a pivotal role in tumor cell invasion. Invadopodia are actin-rich membrane protrusions formed by tumor cells that degrade the extracellular matrix for invasion. Depletion of the exocyst component Exo70 or Sec8 led to failure in invadopodia formation in MDA-MB-231 cells iv expressing constitutively active c-Src, whereas the overexpression of Exo70 promoted invadopodia formation. Disrupting the exocyst function by RNA interference of EXO70 or SEC8, or by expression of a dominant negative fragment of Exo70 blocked the secretion of matrix metalloproteinases. I further found that the exocyst interacts with the Arp2/3 complex in cells with high invasion potential; blocking the exocyst-Arp2/3 interaction inhibited Arp2/3-mediated actin polymerization and invadopodia formation. Finally, the exocyst also functions in directly regulating Arp2/3-mediated actin polymerization. Using pyrene actin assay and total internal reflection fluorescence microscopy, I found that Exo70 synergizes with WAVE2 to promote Arp2/3-mediated actin polymerization and branching. In addition, I have examined how the Exo70-Arp2/3 interaction is regulated in the cell downstream of growth factor signaling. Overall, these studies provide mechanistic insights to the function of the exocyst in exocytosis and cell migration. v Table of Contents Chapter 1. Introduction································································································· 1 1.1 Overview··············································································································· 1 1.2 The exocyst complex···························································································· 3 1.3 Phosphoinositides in cell regulation and membrane dynamics·························· 56 1.4 Cell invasion and invadopodia structures··························································· 60 1.5 Thesis overview··································································································
Load more

Recommended publications
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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 .
    [Show full text]
  • 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.
    [Show full text]
  • Synaptic Vesicle Dynamics in Living Cultured Hippocampal Neurons Visualized with CY3-Conjugated Antibodies Directed Against the Lumenal Domain of Synaptotagmin
    The Journal of Neuroscience, June 1995, 1~76): 4328-4342 Synaptic Vesicle Dynamics in Living Cultured Hippocampal Neurons Visualized with CY3-Conjugated Antibodies Directed against the Lumenal Domain of Synaptotagmin Kajetan Kraszewski,’ Olaf Mundigl,’ Laurie DanielI,’ Claudia Verclerio,* Michela Matteoli,2 and Pietro De Camilli’ ‘Department of Cell Biology and Howard Hughes Medical Institute, Yale University School Medicine, New Haven, Connecticut 06510 and XNR Center of Cytopharmacology and Department of Medical Pharmacology, University of Milano, Milano, Italy Antibodies directed against the lumenal domain of synap- which representthe presynaptic elementsof synapses.They un- totagmin I conjugated to CY3 (CYB-Syt,-Abs) and video mi- dergo exocytosis selectively at specialized regions of the pre- croscopy were used to study the dynamics of synaptic ves- synaptic plasmalemmacalled active zones and their rate of exo- icles in cultured hippocampal neurons. When applied to cytosis is dramatically stimulated by depolarization-induced cultures after synapse formation, CY3-Syt,-Abs produced a Ca2+ influx (De Camilli and Jahn, 1990; Jesse1and Kandel, strong labeling of presynaptic vesicle clusters which was 1992; Stidhof et al., 1993; Bennett and Scheller, 1994). markedly increased by membrane depolarization. The in- Until recently, the properties of SVs in situ could only be crease of the rate of CYSSyt,-Ab uptake in a high K+ me- studied by conventional morphological approacheswhich in- dium was maximal during the first few minutes but per- volve cell fixation, or by using electrophysiological techniques sisted for as long as 60 min. In axons developing in iso- which detect effects produced by neurotransmitterrelease. New lation, CYSSyt,-Abs, in combination with electron micros- probes have now been developed which make possibleto mon- copy immunocytochemistry, revealed the presence of itor morphologically, at the light microscopic level, SV dynam- synaptic vesicle clusters which move in bulk in antero- ics in the living cell.
    [Show full text]
  • Stochastic Modeling of Nanoparticle Internalization and Expulsion Through Receptor-Mediated Transcytosis
    Nanoscale Stochastic Modeling of Nanoparticle Internalization and Expulsion through Receptor-mediated Transcytosis Journal: Nanoscale Manuscript ID NR-ART-03-2019-002710.R1 Article Type: Paper Date Submitted by the 23-Apr-2019 Author: Complete List of Authors: Deng, Hua; Washington State University, School of Mechanical and Materials Engineering Dutta, Prashanta; Washington State University, School of Mechanical and Materials Engineering Liu, Jin; Washington State University, School of Mechanical and Materials Engineering Page 1 of 10 Please doNanoscale not adjust margins Nanoscale ARTICLE Stochastic Modeling of Nanoparticle Internalization and Expulsion through Receptor-mediated Transcytosis a a a Received 00th January 20xx, Hua Deng Prashnanta Dutta and Jin Liu * Accepted 00th January 20xx The receptor-mediated transcytosis (RMT) is a fundamental mechanism for the transcellular transport of nanoparticles. RMT DOI: 10.1039/x0xx00000x is a complex process, during which the nanoparticles actively interact with the membrane and the membrane profile undergoes extreme deformations for particle internalization and expulsion. In this work, we developed a stochastic model to study the endocytosis and exocytosis of nanoparticle across soft membranes. The model is based on the combination of a stochastic particle binding model with a membrane model, and accounts for both the clathrin-mediated endocytosis for internalization and the actin-mediated exocytosis for explusion. Our results showed the nanoparticle must have certain avidity with enough ligand density and ligand-receptor binding affinity to be uptaken, while too much avidity limited the particle release from the cell surface. We furhter explored the functional roles of actin during exocytosis, which has been a topic under active debates. Our simulations indicated that the membrane compression due to the actin induced tension tended to break the ligand-receptor bonds and to shrink the fusion pore.
    [Show full text]
  • Bio102 Problems Transport Across Membranes
    Bio102 Problems Transport Across Membranes 1. Antiport is one type of A. facilitated transport. B. active transport. C. endocytosis. D. channel protein. E. carrier protein. 2. Pinocytosis is one type of A. exocytosis. B. phagocytosis. C. facilitated transport. D. endocytosis. E. diffusion. 3A. Consider a bacterial cell that is hypertonic in comparison to its environment. Will water move into the cell or out of the cell? 3B. We now add a large amount of either O2, N2, or Pyruvate to the fluid surrounding the cell. Which one will have the biggest effect on the movement of water? Will its addition increase or decrease the movement of water? Please explain your answer. 4. Imagine a bacterial cell living in a test tube under the following conditions: K+ Mg2+ Na+ inside the cell 50 mM 0.1 mM 10 mM outside the cell 10 mM 3 mM 150 mM 4A. Is the G value for Mg2+ movement into the cell positive, negative or zero? 4B. Under these conditions, is the solution hypotonic, hypertonic or isotonic relative to the cell? 4C. Under these conditions, will the net movement of water be into the cell or out of the cell? Why? 4D. If we added a large concentration (say, 1M) of CO2 to the outside of the cell, it would have no effect on the net movement of water. Why not? 4E. If the fatty acid tails in the phospholipids that make up this cell’s membranes were more saturated, would that increase or decrease the rate at which water moves? Or would it have no effect? Please explain.
    [Show full text]
  • Membrane Trafficking and Vesicle Fusion Post-Palade Eraresearchers Winthenobel Prize
    GENERAL ARTICLE Membrane Trafficking and Vesicle Fusion Post-Palade EraResearchers WintheNobel Prize Riddhi Atul Jani and Subba Rao Gangi Setty The functions of the eukaryotic cell rely on membrane- bound compartments called organelles. Each of these possesses dis- tinct membrane composition and unique function. In the 1970’s, during George Palade’s time, it was unclear how these organelles communicate with each other and perform their biological functions. The elegant research work of James E (left) Riddhi Atul Jani is a Rothman, Randy W Schekman and Thomas C Südhof identi- graduate student in Subba fied the molecular machinery required for membrane traf- Rao’s Lab at MCB, IISc. She is interested in ficking, vesicle fusion and cargo delivery. Further, they also studying the SNARE showed the importance of these processes for biological func- dynamics during melano- tion. Their novel findings helped to explain several biological some biogenesis. phenomena such as insulin secretion, neuron communication (right) Subba Rao Gangi and other cellular activities. In addition, their work provided Setty is an Assistant clues to cures for several neurological, immunological and Professor at the MCB, metabolic disorders. This research work laid the foundation IISc, Bangalore. He is interested in understand- to the field of molecular cell biology and these post-Palade ing the disease associated investigators were awarded the Nobel Prize in Physiology or protein trafficking Medicine in 2013. pathways in mammalian cells. Introduction Membrane Transport: In the eukaryotic cell, a majority of proteins are made in the cytosol. But the transmembrane and secretory proteins are synthesized in an organelle called the rough endoplasmic reticulum (ER).
    [Show full text]
  • Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: the Autophagic- and Endo-Lysosomal Systems Go Extracellular
    International Journal of Molecular Sciences Review Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular 1, 1, 1,2 1 3 Sandra Buratta y, Brunella Tancini y, Krizia Sagini , Federica Delo , Elisabetta Chiaradia , Lorena Urbanelli 1,* and Carla Emiliani 1,4,* 1 Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, Italy; [email protected] (S.B.); [email protected] (B.T.); [email protected] (K.S.); [email protected] (F.D.) 2 Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Montebello, Oslo, Norway 3 Department of Veterinary Medicine, University of Perugia, Via S. Costanzo 4, 06126 Perugia, Italy; [email protected] 4 Centro di Eccellenza sui Materiali Innovativi Nanostrutturati (CEMIN), University of Perugia, Via del Giochetto, 06123 Perugia, Italy * Correspondence: [email protected] (L.U.); [email protected] (C.E.); Tel.: +39-075-585-7440 (L.U.); +39-075-585-7438 (C.E.); Fax: +39-075-585-7436 (L.U. & C.E.) Both authors contributed equally to this work. y Received: 17 March 2020; Accepted: 6 April 2020; Published: 8 April 2020 Abstract: Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis.
    [Show full text]
  • Glossary.Pdf
    Glossary Pronunciation Key accessory fruit A fruit, or assemblage of fruits, adaptation Inherited characteristic of an organ- Pronounce in which the fleshy parts are derived largely or ism that enhances its survival and reproduc- a- as in ace entirely from tissues other than the ovary. tion in a specific environment. – Glossary Ј Ј a/ah ash acclimatization (uh-klı¯ -muh-tı¯-za -shun) adaptive immunity A vertebrate-specific Physiological adjustment to a change in an defense that is mediated by B lymphocytes ch chose environmental factor. (B cells) and T lymphocytes (T cells). It e¯ meet acetyl CoA Acetyl coenzyme A; the entry com- exhibits specificity, memory, and self-nonself e/eh bet pound for the citric acid cycle in cellular respi- recognition. Also called acquired immunity. g game ration, formed from a fragment of pyruvate adaptive radiation Period of evolutionary change ı¯ ice attached to a coenzyme. in which groups of organisms form many new i hit acetylcholine (asЈ-uh-til-ko–Ј-le¯n) One of the species whose adaptations allow them to fill dif- ks box most common neurotransmitters; functions by ferent ecological roles in their communities. kw quick binding to receptors and altering the perme- addition rule A rule of probability stating that ng song ability of the postsynaptic membrane to specific the probability of any one of two or more mu- o- robe ions, either depolarizing or hyperpolarizing the tually exclusive events occurring can be deter- membrane. mined by adding their individual probabilities. o ox acid A substance that increases the hydrogen ion adenosine triphosphate See ATP (adenosine oy boy concentration of a solution.
    [Show full text]
  • The Exocyst Complex in Health and Disease
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector REVIEW published: 12 April 2016 doi: 10.3389/fcell.2016.00024 The Exocyst Complex in Health and Disease Magdalena Martin-Urdiroz, Michael J. Deeks, Connor G. Horton, Helen R. Dawe and Isabelle Jourdain * Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK Exocytosis involves the fusion of intracellular secretory vesicles with the plasma membrane, thereby delivering integral membrane proteins to the cell surface and releasing material into the extracellular space. Importantly, exocytosis also provides a source of lipid moieties for membrane extension. The tethering of the secretory vesicle before docking and fusion with the plasma membrane is mediated by the exocyst complex, an evolutionary conserved octameric complex of proteins. Recent findings indicate that the exocyst complex also takes part in other intra-cellular processes besides secretion. These various functions seem to converge toward defining a direction of Edited by: Mary Munson, membrane growth in a range of systems from fungi to plants and from neurons to cilia. University of Massachusetts Medical In this review we summarize the current knowledge of exocyst function in cell polarity, School, USA signaling and cell-cell communication and discuss implications for plant and animal health Reviewed by: and disease. Viktor Zarsky, Charles University, Czech Republic Keywords: exocyst complex, fungi, plants, mammals, pathogens Charles Andrew Yeaman, University of Iowa Carver College of Medicine, USA INTRODUCTION Meritxell Riquelme, Centro de Investigación Científica y de Exocytosis involves the fusion of intracellular secretory vesicles with the plasma membrane (PM), Educación Superior de Ensenada, Mexico thereby delivering integral membrane proteins at the cell surface and releasing material into the extracellular space, such as hormones or components of the extracellular matrix.
    [Show full text]