Brodsky, FM

Stow, JL

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UCL Discovery

  Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website.  Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.  Current Opinion in Cell Biology 2020,65:iii–vThis overview comes from a themed issue onMembrane TraffickingEdited by Frances M. Brodsky and JenniferL. Stowhttps://doi.org/10.1016/j.ceb.2020.09.0030955-0674/© 2020 Published by Elsevier Ltd.Frances M. BrodskyDivision of Biosciences, University CollegeLondon, Gower Street, London, WC1E 6BT,UK*Corresponding author: Brodsky, Frances M.e-mail: f.brodsky@ucl.ac.ukProf. Frances Brodsky is Director of the Divi-sion of Biosciences at UCL. Her laboratoryfocuses on how intracellular clathrin-mediatedpathways influence glucose metabolism, theimmune system, and neuronal function. Thisresearch, currently supported by the Well-come Trust and the UKRI, emerges from acareer studying the biochemistry, genetic di-versity, and evolution of clathrin proteins, atthe University of California, San Francisco,until 2014, then at UCL.Jennifer L. StowInstitute for Molecular Bioscience, The Uni-versity of Queensland, Brisbane, QLD,4072, Australia*Corresponding author: Stow, Jennifer L.e-mail: j.stow@imb.uq.edu.auProf. Jenny Stow is a group leader, NHMRCLeadership Research Fellow, Deputy Director(Research), and head of IMB microscopy, atIMB, the University of Queensland. Herresearch has explored both secretory andendocytic pathways in epithelial cells andmacrophages, using live cell imaging andbiochemistry to uncover GTPases, SNAREs,scaffolds, and kinases as key regulators ofinflammation and disease.Available online at www.sciencedirect.comScienceDirectwww.sciencedirect.comEditorial overview: Membrane traffic in the time ofCOVID-19Frances M. Brodsky and Jennifer L. StowWe write this editorial emerging from lockdown in countries across theworld in the face of the COVID-19 pandemic. These have been chal-lenging, frightening, and too often catastrophic times for many. Such timeslead to evaluation of one’s own enterprise in the context of a globalemergency. The mandated reliance of the world on scientific data andjudgment has now placed research that has often been treated by gov-ernments as obscure, in these increasingly anti-intellectual times, atcenter stage. We hope that a silver lining to the current pandemic will be arenewed recognition of the place of science in society and redoubled ef-forts by governments to appropriately fund and support scientific researchthat will protect us now and into the future.As the pandemic has evolved, the use of modeling and mathematicalepidemiology and our knowledge of coronavirus biology and human im-munity have directly impacted government and medical decisions. Thesefields absolutely rely on a foundation of fundamental cell and molecularbiology, biochemistry, and microbiology, and an advanced understanding ofmembrane traffic is needed for insights into how and where SARS-CoV-2infects different human cells and how our immune system responds to theinfection. Likewise, research on membrane traffic was vital over the pastdecades for understanding the pathogenesis of HIV [1], and new insightsinto clathrin-mediated transport [2] and how it is subverted by HIV [3e5]will continue to inform the development of effective treatments. Indeed,many of the historical and recent discoveries in membrane traffic haveemerged from studies using viruses, bacteria, and other pathogens as toolsto probe cell pathways and molecular mechanisms (reviewed in this issueby Noack and Mukherjee [6]). The articles in this issue were written inthe period just before the global escalation of COVID-19, and the sciencethey review is highly topical for the field of membrane traffic. However,they will also be vital for current investigations around the world to un-derstand SARS-CoV-2, its mode of infection in different tissues, diseasemanifestations, and resulting immune responses and for the developmentof vaccines and treatments.The reviews selected for this issue are written by experts across membranetraffic, contemporizing issues such as sorting, sensing, scaffolding, andrecognition of proteins, lipids, and cargo in trafficking pathways. OrganelleCurrent Opinion in Cell Biology 2020, 65:iii–viv Membrane traffickingformation, regulation, and interactions are surveyed.Importantly, environmental, metabolic, and microbicidalinfluences on membrane traffic and vice versa are alsoappraised and updated. Here we summarize theemerging themes in membrane traffic covered by thereviews in this issue. We sincerely thank the authors fortheir comprehensive updates, expert insights, and theirongoing, pioneering research contributions.While membrane traffic focuses on mechanisms ofintracellular transport, the end result of import andexport of membrane-associated proteins and of mem-brane itself is to influence the interaction of cells withtheir environment. The importance of mechanosensingin this process and the involvement of membrane trafficin response to membrane stress or injury is highlightedin several reviews in this issue. The review byVassilopoulos [7] describes membrane traffic pathwaysin muscle cells, which have caveolae and clathrin-coatedplaques to help manage intense stress at membranesand have dysferlin-mediated mechanisms for constantrepair. Bohannan and Hanson [8] discuss roles forESCRT proteins and calcium in repair of both internaland external membrane injury from pathogens, partic-ulates, and metabolic or chemical stresses. The reviewby Parton et al [9] is focused on the molecular mecha-nisms of caveolae formation, discussing how thesestructures regulate membrane tension and respond toUV-induced stress through rapid disassembly. Babst [10]describes how lipid fluidity in the yeast membrane, inresponse to environmental changes, alters the mem-brane traffic of nutrient transporters during metabolicstress, focusing on how eisosome formation regulatestransporters. The review by Day and Stachowiak [11]discusses the biophysical requirements for membranebending and considers how the influence of cargo onlipid fluidity leads to the recruitment and necessarycombination of different mechanical forces to regulatemembrane curvature and vesiculation during membranetraffic.Nutrient availability is a significant stress that regulatesmembrane traffic in a variety of pathways. Bryant andGould [12] take a broad view of the trafficking andtranslocation leading to insulin-induced GLUT4 clear-ance of blood glucose. Their review considers how thistrafficking is dictated by physiological determinants andmetabolic needs, which vary across cell types and acrossspecies. As an intracellular starvation response, auto-phagosome formation from phagophore assembly sites isreviewed by Hollstein and Kraft [13] with updates onmolecular regulation and the roles of the endoplasmicreticulum and vacuoles in autophagy. Microenviron-mental triggers, nutrient stress, and gene mutations caninduce the uptake of fluid, nutrients, and debris bymacropinocytosis. Stow et al [14] review newly identi-fied molecular regulators in immune cells and cancerCurrent Opinion in Cell Biology 2020, 65:iii–vcells that govern macropinosome formation and down-stream cargo sorting, receptor signaling, and cell survival.Interactions between organelles mediated by lipid ex-change and lipid regulation, which were highlighted inVolume 59 in this series, continue as very active areas inmembrane traffic. Here the review by Lees and Reinisch[15] provides new perspectives on the molecules thatregulate lipid exchange at organelle contact sites.Harper et al [16] provide updates on the protein com-plexes that mediate small-molecule exchange betweenmitochondria and other organelles and the review fromvan den Boomen et al [17] addresses regulation of sterolhomeostasis by ubiquitination.Cargo sorting at appropriate cellular locations has been atheme of membrane traffic since the discovery of coatproteins and their ability to select cargo for sequestra-tion. The importance of sorting integrity to the health ofa whole organism, as well to the function of a single cell,is becoming increasingly apparent. The recent progressin understanding regulation of clathrin-coated vesicleformation reviewed by Briant et al [2] demonstrates howclathrin-mediated pathways affect tissue developmentand differentiation, as well as disease. The review byPhillips et al [18] discusses quality control mechanismsin the endoplasmic reticulum that are absolutely criticalfor the health of a cell and whose malfunction accountsfor toxicity in protein folding diseases. The formation ofprotein sorting domains and tubules on endosomes forselective degradation or recycling is emerging as a keymechanism of cargo sorting, as described at the molec-ular and structural levels in the review by Weeratungaet al [19] and as reviewed for the endosomal pathwayof C. elegans by Norris and Grant [20].Sorting and trafficking of cargo in the secretory pathwayand moving through the Golgi have been studied by liveimaging, and the revelations from such studies arereviewed here by Thomas and Fromme [21], with afocus on Rab GTPase cascades and counter currents thatregulate this transport. The review by Shafaq-Zadahet al [22] provides a comprehensive update onclathrin-independent pathways for endocytosis thatcontribute to apico-basolateral polarity in epithelia,front-rear polarity in migrating cells, and synapse for-mation in neurons and immune cells. The review high-lights how these endocytic pathways coordinate withsecretory traffic to deploy proteins to specific membranedomains in a highly targeted fashion. Continuing on thetheme of highly targeted traffic, Naslavsky and Caplan[23] review endocytic traffic that helps to regulate or-ganelles without membranes, such as cilia and thecentrosome, which are supported by endocytic ma-chinery throughout the cell cycle. The review by NoackandMukherjee [6] highlights recent examples of sortingand trafficking events that are highjacked by bacterialwww.sciencedirect.comCoronavirus disease 2019 Brodsky and Stow vand viral pathogens, including mechanisms for subvert-ing traffic at the level of the endoplasmic reticulum andin mitophagy.We close this editorial with a heartfelt tribute to threegiants in the membrane traffic field whom we have lostduring this past year, both to COVID-19 and to cancer,Marilyn Farquhar, Kathryn Howell, and Ernst Unge-wickell. The career contributions of Marilyn andKathryn laid much of the foundation for our currentunderstanding of the ultrastructure, pathways, andmolecules of the Golgi apparatus [24,25]. Ernst was apioneer in the field of clathrin biochemistry, from hisidentification of clathrin’s triskelion morphology [26] tohis in vitro reconstitution of clathrin coat formation[27]. All three were strong characters, of staunchintegrity, with passion for their research. They leave alegacy of several generations of trainees who continue topush the field of membrane traffic forward. And theirwork, similar to much of that described in this issue, hasset the stage for progress in molecular biology that willeventually overcome the diseases that removed themfrom our community.References1. Balasubramaniam M, Freed EO: New insights into HIV as-sembly and trafficking. Physiology (Bethesda) 2011, 26:236–251.2. Briant K, Redlingshöfer L, Brodsky FM: Clathrin’s life beyond40: connecting biochemistry with physiology and disease.Curr Opin Cell Biol 2020, 65:141–149.3. Morris KL, Buffalo CZ, Sturzel CM, Heusinger E, Kirchhoff F,Ren X, Hurley JH: HIV-1 nefs are cargo-sensitive AP-1 trime-rization switches in tetherin downregulation. Cell 2018, 174:659–671.4. Buffalo CZ, Stürzel CM, Heusinger E, Kmiec D, Kirchhoff F,Hurley JH, Ren X: Structural basis for tetherin antagonism asa barrier to zoonotic lentiviral transmission. Cell Host Microbe2019, 26:359–368.5. Tavares LA, de Carvalho JV, Costa CS, Silveira RM, deCarvalho AN, Donadi EA, daSilva LLP: Two functional variantsof AP-1 complexes composed of either g2 or g1-subunits areindependently required for MHC-I downregulation by HIV-1Nef. J Virol 2020, 94. JVI 02039-02019.6. Noack J, Mukherjee S: “Make way”: pathogen exploitation ofmembrane traffic. Curr Opin Cell Biol 2020, 65:78–85.7. Vassilopoulos S: Unconventional roles for membrane trafficproteins in response to muscle membrane stress. Curr OpinCell Biol 2020, 65:42–49.www.sciencedirect.com8. Bohannon KP, Hanson PI: ESCRT puts its thumb on thenanoscale: fixing tiny holes in endolysosomes. Curr Opin CellBiol 2020, 65:122–130.9. Parton RG, McMahon KA, Wu Y: Caveolae: formation, dy-namics, and function. Curr Opin Cell Biol 2020, 65:8–16.10. Babst M: Regulation of nutrient transporters by metabolic andenvironmental stresses. Curr Opin Cell Biol 2020, 65:35–41.11. Day KJ, Stachowiak JC: Biophysical forces in membranebending and traffic. Curr Opin Cell Biol 2020, 65:72–77.12. Bryant NJ, Gould GW: Insulin stimulated GLUT4 translocation– size is not everything! Curr Opin Cell Biol 2020, 65:28–34.13. Hollenstein DM, Kraft C: Autophagosomes are formed at adistinct cellular structure. Curr Opin Cell Biol 2020, 65:50–57.14. Stow JL, Hung Y, Wall AA: Macropinocytosis: insights fromimmunology and cancer. Curr Opin Cell Biol 2020, 65:131–140.15. Lees JA, Reinisch KM: Inter-organelle lipid transfer: a channelmodel for Vps13 and chorein-N motif proteins. Curr Opin CellBiol 2020, 65:66–71.16. Harper CS, White AJ, Lackner LL: The multifunctional nature ofmitochondrial contact site proteins. Curr Opin Cell Biol 2020,65:58–65.17. van den Boomen DJH, Volkmar N, Lehner PJ: Ubiquitin-medi-ated regulation of sterol homeostasis. Curr Opin Cell Biol2020, 65:103–111.18. Phillips BP, Gomez-Navarro N, Miller EA: Protein quality controlin the endoplasmic reticulum. Curr Opin Cell Biol 2020, 65:96–102.19. Weeratunga S, Paul B, Collins BM: Recognising the signals forendosomal trafficking. Curr Opin Cell Biol 2020, 65:17–27.20. Norris A, Grant BD: Endosomal microdomains: formation andfunction. Curr Opin Cell Biol 2020, 65:86–95.21. Thomas LL, Fromme CJ: Extensive GTPase crosstalk regu-lates Golgi trafficking and maturation. Curr Opin Cell Biol 2020,65:1–7.22. Shafaq-Zadah M, Dransart E, Johannes L: Clathrin-independentendocytosis, retrograde trafficking, and cell polarity. CurrOpin Cell Biol 2020, 65:112–121.23. Naslavsky N, Caplan S: Endocytic membrane trafficking in thecontrol of centrosome function. Curr Opin Cell Biol 2020, 65:150–155.24. Farquhar MG, Palade GE: The Golgi apparatus: 100 years ofprogress and controversy. Trends Cell Biol 1998, 8:2–10.25. Mogelsvang S, Marsh BJ, Ladinsky MS, Howell KE: Predictingfunction from structure: 3D structure studies of themammalian Golgi complex. Traffic 2004, 5:338–345.26. Ungewickell E, Branton D: Assembly units of clathrin coats.Nature 1981, 289:420–422.27. Dannhauser PN, Ungewickell EJ: Reconstitution of clathrin-coated bud and vesicle formation with minimal components.Nat Cell Biol 2012, 14:634–639.Current Opinion in Cell Biology 2020, 65:iii–v

Editorial overview: Membrane traffic in the time of COVID-19

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Editorial overview: Membrane traffic in the time of COVID-19

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