Regulation of surface coat exchange by differentiating African trypanosomes

Amy E Gruszynski, Frederick J van Deursen, Maria C Albareda, Alexander Best, Kshitiz Chaudhary, Laura J Cliffe, Laura del Rio, Joe Dan Dunn, Louise Ellis, Krystal J Evans, Juliana M Figueiredo, Nicholas A Malmquist, Yusuf Omosun, Jennifer B Palenchar, Sara Prickett, George A Punkosdy, Giel van Dooren, Qian Wang, Anant K Menon, Keith R MatthewsJames D Bangs

Research output: Contribution to journalArticlepeer-review

Abstract

African trypanosomes (Trypanosoma brucei) have a digenetic lifecycle that alternates between the mammalian bloodstream and the tsetse fly vector. In the bloodstream, replicating long slender parasites transform into non-dividing short stumpy forms. Upon transmission into the fly midgut, short stumpy cells differentiate into actively dividing procyclics. A hallmark of this process is the replacement of the bloodstream-stage surface coat composed of variant surface glycoprotein (VSG) with a new coat composed of procyclin. Pre-existing VSG is shed by a zinc metalloprotease activity (MSP-B) and glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC). We now provide a detailed analysis of the coordinate and inverse regulation of these activities during synchronous differentiation. MSP-B mRNA and protein levels are upregulated during differentiation at the same time as proteolysis whereas GPI-PLC levels decrease. When transcription or translation is inhibited, VSG release is incomplete and a substantial amount of protein stays cell-associated. Both modes of release are still evident under these conditions, but GPI hydrolysis plays a quantitatively minor role during normal differentiation. Nevertheless, GPI biosynthesis shifts early in differentiation from a GPI-PLC sensitive structure to a resistant procyclic-type anchor. Translation inhibition also results in a marked increase in the mRNA levels of both MSP-B and GPI-PLC, consistent with negative regulation by labile protein factors. The relegation of short stumpy surface GPI-PLC to a secondary role in differentiation suggests that it may play a more important role as a virulence factor within the mammalian host.
Original languageEnglish
Pages (from-to)211-23
Number of pages13
JournalMolecular and Biochemical Parasitology
Volume147
Issue number2
DOIs
Publication statusPublished - 2006

Fingerprint

Dive into the research topics of 'Regulation of surface coat exchange by differentiating African trypanosomes'. Together they form a unique fingerprint.

Cite this