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

doi:10.1073/pnas.0501886102

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 language	English
Pages (from-to)	8716-8721
Number of pages	6
Journal	Proceedings of the National Academy of Sciences (PNAS)
Volume	102
Issue number	24
DOIs	https://doi.org/10.1073/pnas.0501886102
Publication status	Published - 14 Jun 2005

Keywords / Materials (for Non-textual outputs)

Antigenic variation
Trypanosoma brucei

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10.1073/pnas.0501886102

Cite this

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title = "Variant surface glycoprotein RNA interference triggers a precytokinesis cell cycle arrest in African trypanosomes",

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 (",

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doi = "10.1073/pnas.0501886102",

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T1 - Variant surface glycoprotein RNA interference triggers a precytokinesis cell cycle arrest in African trypanosomes

AU - Sheader, Karen

AU - Vaughan, Sue

AU - Minchin, James

AU - Hughes, Katie

AU - Gull, Keith

AU - Rudenko, Gloria

PY - 2005/6/14

Y1 - 2005/6/14

N2 - 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 (

AB - 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 (

KW - Antigenic variation

KW - Trypanosoma brucei

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U2 - 10.1073/pnas.0501886102

DO - 10.1073/pnas.0501886102

M3 - Article

C2 - 15937117

AN - SCOPUS:20844442483

SN - 0027-8424

VL - 102

SP - 8716

EP - 8721

JO - Proceedings of the National Academy of Sciences (PNAS)

JF - Proceedings of the National Academy of Sciences (PNAS)

IS - 24

ER -

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

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