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Cytokinesis of Trypanosoma brucei bloodstream forms depends on expression of adenylyl cyclases of the ESAG4 or ESAG4-like subfamily.
Mol Microbiol. 2012 Apr; 84(2):225-42
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16 Apr 2012
New Finding
DOI: 10.3410/f.14264958.15777403
This elegant work demonstrates that knockdown of an adenylyl cyclase (AC) subfamily in Trypanosoma brucei (ESAG4/ESAG4L) induces a lethal phenotype linked to impaired cytokinesis. Trypanosomes possess a number of enzymes involved in cyclic AMP metabolism, but the signaling function of this second messenger...Continue reading
This elegant work demonstrates that knockdown of an adenylyl cyclase (AC) subfamily in Trypanosoma brucei (ESAG4/ESAG4L) induces a lethal phenotype linked to impaired cytokinesis. Trypanosomes possess a number of enzymes involved in cyclic AMP metabolism, but the signaling function of this second messenger is not completely understood. This is the first study showing that knockdown of the expression of some of the more than 80 genes coding for ACs causes a lethal effect.
In contrast, knockout of the expression site-associated AC gene (ESAG4) does not affect parasite growth in vitro or in vivo due to a compensatory upregulation of redundant ESAG4-like genes.
In contrast, knockout of the expression site-associated AC gene (ESAG4) does not affect parasite growth in vitro or in vivo due to a compensatory upregulation of redundant ESAG4-like genes.
Disclosures
None declared
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Docampo R: F1000Prime Recommendation of [Salmon D et al., Mol Microbiol 2012, 84(2):225-42]. In F1000Prime, 16 Apr 2012; DOI: 10.3410/f.14264958.15777403. F1000Prime.com/14264958#eval15777403
F1000Prime Recommendations, Dissents and Comments for [Salmon D et al., Mol Microbiol 2012, 84(2):225-42]. In F1000Prime, 24 May 2013; F1000Prime.com/14264958
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Antigenic variation of the parasite Trypanosoma brucei operates by monoallelic expression of a variant surface glycoprotein (VSG) from a collection of multiple telomeric expression sites (ESs). Each of these ESs harbours a long polycistronic transcription unit containing several expression site-associated genes (ESAGs). ESAG4 copies encode bloodstream stage-specific adenylyl cyclases (AC) and belong to a larger gene family of around 80 members, the majority of which, termed genes related to ESAG4 (GRESAG4s), are not encoded in ESs and are expressed constitutively in the life cycle. Here we report that ablation of ESAG4 from the active ES did not affect parasite growth, neither in culture nor upon rodent infection, and did not significantly change total AC activity. In contrast, inducible RNAi-mediated knock-down of an AC subfamily that includes ESAG4 and two ESAG4-like GRESAG4 (ESAG4L) genes, decreased total AC activity and induced a lethal phenotype linked to impaired cytokinesis. In the Δesag4 line compensatory upregulation of apparently functionally redundant ESAG4L genes was observed, suggesting that the ESAG4/ESAG4L-subfamily ACs are involved in the control of cell division. How deregulated adenylyl cyclases or cAMP might impair cytokinesis is discussed.
© 2012 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2958.2012.08013.x
PMID: 22340731
