학술논문
Regulation of surface coat exchange by differentiating African trypanosomes
Document Type
Article
Author
Gruszynski, Amy E.; van Deursen, Frederick J.; Albareda, Maria C.; Best, Alexander; Chaudhary, Kshitiz; Cliffe, Laura J.; del Rio, Laura; Dunn, Joe Dan; Ellis, Louise; Evans, Krystal J.; Figueiredo, Juliana M.; Malmquist, Nicholas A.; Omosun, Yusuf; Palenchar, Jennifer B.; Prickett, Sara; Punkosdy, George A.; van Dooren, Giel; Wang, Qian; Menon, Anant K.; Matthews, Keith R.
Source
Subject
*TRYPANOSOMA
*PARASITES
*MESSENGER RNA
*AFRICAN trypanosomiasis
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Language
ISSN
0166-6851
Abstract
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. [Copyright &y& Elsevier]