An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids
Authors:Harriet Allison1, Amanda J. O’Reilly1, Jeremy Sternberg2 and Mark C. Field1
1 Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, Scotland, DD1 5EH.
2 School of Biological Sciences, University of Aberdeen, Aberdeen, AB24 2TZ, UK.
Keywords:
Trypanosoma brucei, protein sorting, exocytosis, variant surface glycoprotein, endoplasmic reticulum, evolution, trypanosome.
Abbreviations: ER - endoplasmic reticulum, ERGIC - ER-Golgi intermediate compartment, IGPs - invariant glycoproteins, ISG - invariant surface glycoprotein, PAD1/2 - protein associated with differentiation 1/2, TMD - trans-membrane domain, VSG - variant surface glycoprotein.
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Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Harriet Allison, Amanda J. O’Reilly, Jeremy Sternberg and Mark C. Field (2014). An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids. Microbial Cell 1(10): 325-345.
© 2014 Allison et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
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. In T. 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 from T. b. rhodesiense infected 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.
doi: 10.15698/mic2014.10.170
Volume 1, pp. 325 to 345, published 01/10/2014.