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      Lipids in host–pathogen interactions: Pathogens exploit the complexity of the host cell lipidome

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          Abstract

          Lipids were long believed to have a structural role in biomembranes and a role in energy storage utilizing cellular lipid droplets and plasma lipoproteins. Research over the last decades has identified an additional role of lipids in cellular signaling, membrane microdomain organization and dynamics, and membrane trafficking. These properties make lipids an attractive target for pathogens to modulate host cell processes in order to allow their survival and replication. In this review we will summarize the often ingenious strategies of pathogens to modify the lipid homeostasis of host cells, allowing them to divert cellular processes. To this end pathogens take full advantage of the complexity of the lipidome. The examples are categorized in generalized and emerging principles describing the involvement of lipids in host–pathogen interactions. Several pathogens are described that simultaneously induce multiple changes in the host cell signaling and trafficking mechanisms. Elucidation of these pathogen-induced changes may have important implications for drug development. The emergence of high-throughput lipidomic techniques will allow the description of changes of the host cell lipidome at the level of individual molecular lipid species and the identification of lipid biomarkers.

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          Regulated portals of entry into the cell.

          The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
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            Membrane recognition by phospholipid-binding domains.

            Many different globular domains bind to the surfaces of cellular membranes, or to specific phospholipid components in these membranes, and this binding is often tightly regulated. Examples include pleckstrin homology and C2 domains, which are among the largest domain families in the human proteome. Crystal structures, binding studies and analyses of subcellular localization have provided much insight into how members of this diverse group of domains bind to membranes, what features they recognize and how binding is controlled. A full appreciation of these processes is crucial for understanding how protein localization and membrane topography and trafficking are regulated in cells.
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              Virus Entry: Open Sesame

              Detailed information about the replication cycle of viruses and their interactions with host organisms is required to develop strategies to stop them. Cell biology studies, live-cell imaging, and systems biology have started to illuminate the multiple and subtly different pathways that animal viruses use to enter host cells. These insights are revolutionizing our understanding of endocytosis and the movement of vesicles within cells. In addition, such insights reveal new targets for attacking viruses before they can usurp the host-cell machinery for replication.

                Author and article information

                Contributors
                Journal
                Prog Lipid Res
                Prog. Lipid Res
                Progress in Lipid Research
                Elsevier Ltd.
                0163-7827
                1873-2194
                26 July 2009
                January 2010
                26 July 2009
                : 49
                : 1
                : 1-26
                Affiliations
                Department of Biochemistry and Cell Biology, Institute of Biomembranes, Utrecht University, P.O. Box 80176, 3508 TD Utrecht, The Netherlands
                Author notes
                [* ]Corresponding author. Tel.: +31 30 2535375; fax: +31 30 2535492. j.b.helms@ 123456uu.nl
                [1]

                Both of these authors contributed equally to this manuscript.

                [2]

                Present address: Department of Cell and Developmental Biology, CRG-Centre de Regulació Genòmica, C/. Dr. Aiguader, 88 08003 Barcelona, Spain.

                Article
                S0163-7827(09)00031-9
                10.1016/j.plipres.2009.07.003
                7112618
                19638285
                30cc182b-83d2-4477-acfe-6f977944853c
                Copyright © 2009 Elsevier Ltd. All rights reserved.

                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.

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                Categories
                Article

                Biochemistry
                host-pathogen,pathogen vacuole,lipids,phospholipids,lipidomics,lipid droplets,lipid-enriched microdomains,lipid rafts,membrane trafficking,mycobacterium,toxoplasma,clamydia

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