title: Life and times: synthesis, trafficking, and evolution of VSG.
abstract: Evasion of the acquired immune response in African trypanosomes is principally mediated by antigenic variation, the sequential expression of distinct variant surface glycoproteins (VSGs) at extremely high density on the cell surface. Sequence diversity between VSGs facilitates escape of a subpopulation of trypanosomes from antibody-mediated killing. Significant advances have increased understanding of the mechanisms underpinning synthesis and maintenance of the VSG coat. In this review, we discuss the biosynthesis, trafficking, and turnover of VSG, emphasising those unusual mechanisms that act to maintain coat integrity and to protect against immunological attack. We also highlight new findings that suggest the presence of unique or highly divergent proteins that may offer therapeutic opportunities, as well as considering aspects of VSG biology that remain to be fully explored.
authors.affiliation: Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, DD1 5EH, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Manna
authors.affiliation: Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, DD1 5EH, UK.
authors.forename: Cordula
authors.initials: C
authors.lastname: Boehm
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
authors.forename: Ka Fai
authors.initials: KF
authors.lastname: Leung
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
authors.forename: Senthil Kumar
authors.initials: SK
authors.lastname: Natesan
authors.affiliation: Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, DD1 5EH, UK. Electronic address: m.c.field@dundee.ac.uk.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D005075:Biological Evolution; D004705:Endocytosis / Q000502:physiology; D021381:Protein Transport; D014346:Trypanosoma brucei brucei / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D014643:Variant Surface Glycoproteins, Trypanosoma
keywords: Trypanosoma brucei; endocytosis; evolution; exocytosis; protein sorting; protein turnover; variant surface glycoprotein
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