Variant surface glycoprotein RNA interference triggers a precytokinesis cell cycle arrest in African trypanosomes

Karen Sheader, Sue Vaughan, James Minchin, Katie Hughes, Keith Gull, Gloria Rudenko

Research output: Contribution to journalArticlepeer-review

Abstract

Trypanosoma brucei is a protozoan parasite that causes African sleeping sickness. T. brucei multiplies extracellularly in the blood-stream, relying on antigenic variation of a dense variant surface glycoprotein (VSG) coat to escape antibody-mediated lysis. We investigated the role of VSG in proliferation and pathogenicity by using inducible RNA interference to ablate VSG transcript down to 1-2% normal levels. Inhibiting VSG synthesis in vitro triggers a rapid and specific cell cycle checkpoint blocking cell division. Parasites arrest at a discrete precytokinesis stage with two full-length flagella and opposing flagellar pockets, without undergoing additional rounds of S phase and mitosis. A subset (

Original languageEnglish
Pages (from-to)8716-8721
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume102
Issue number24
DOIs
Publication statusPublished - 14 Jun 2005

Keywords

  • Antigenic variation
  • Trypanosoma brucei

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