title: An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids.
abstract: African trypanosomes are evolutionarily highly divergent parasitic protozoa, and as a consequence the vast majority of trypanosome membrane proteins remain uncharacterised in terms of location, trafficking or function. Here we describe a novel family of type I membrane proteins which we designate 'invariant glycoproteins' (IGPs). IGPs are trypanosome-restricted, with extensive, lineage-specific paralogous expansions in related taxa. InT. bruceithree IGP subfamilies, IGP34, IGP40 and IGP48 are recognised; all possess a putative C-type lectin ectodomain and are ER-localised, despite lacking a classical ER-retention motif. IGPs exhibit highest expression in stumpy stage cells, suggesting roles in developmental progression, but gene silencing in mammalian infective forms suggests that each IGP subfamily is also required for normal proliferation. Detailed analysis of the IGP48 subfamily indicates a role in maintaining ER morphology, while the ER lumenal domain is necessary and sufficient for formation of both oligomeric complexes and ER retention. IGP48 is detected by antibodies fromT. b. rhodesienseinfected humans. We propose that the IGPs represent a trypanosomatid-specific family of ER-localised glycoproteins, with potential contributions to life cycle progression and immunity, and utilise oligomerisation as an ER retention mechanism.
authors.affiliation: Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, Scotland, DD1 5EH.
authors.forename: Harriet
authors.initials: H
authors.lastname: Allison
authors.affiliation: Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, Scotland, DD1 5EH.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: O'Reilly
authors.affiliation: School of Biological Sciences, University of Aberdeen, Aberdeen, AB24 2TZ, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sternberg
authors.affiliation: Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, Scotland, DD1 5EH.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
keywords: Trypanosoma brucei; endoplasmic reticulum; evolution; exocytosis; protein sorting; trypanosoma; variant surface glycoprotein