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. doi: 10.1111/j.1365-2958.2012.08013.x. Epub 2012 Mar 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Cluster Analysis
  • Cytokinesis*
  • Gene Deletion
  • Gene Expression
  • Genetic Complementation Test
  • Phylogeny
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Trypanosoma brucei brucei / enzymology*
  • Trypanosoma brucei brucei / genetics
  • Trypanosoma brucei brucei / physiology*

Substances

  • Protozoan Proteins
  • Adenylyl Cyclases