An alternative model for the role of RP2 protein in flagellum assembly in the African trypanosome

Jane Andre, Louise Kerry, Xin Qi, Erica Hawkins, Kristina Drižyte, Michael L. Ginger, Paul G. McKean

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The tubulin cofactor C domain-containing protein TbRP2 is a basal body (centriolar) protein essential for axoneme formation in the flagellate protist Trypanosoma brucei, the causal agent of African sleeping sickness. Here, we show how TbRP2 is targeted and tethered at mature basal bodies and provide novel insight into TbRP2 function. Regarding targeting, understanding how several hundred proteins combine to build a microtubule axoneme is a fundamental challenge in eukaryotic cell biology. We show that basal body localization of TbRP2 is mediated by twinned, N-terminal TOF (TON1, OFD1, and FOP) and LisH motifs, motifs that otherwise facilitate localization of only a few conserved proteins at microtubule-organizing centers in animals, plants, and flagellate protists. Regarding TbRP2 function, there is a debate as to whether the flagellar assembly function of specialized, centriolar tubulin cofactor C domain-containing proteins is processing tubulin, the major component of axonemes, or general vesicular trafficking in a flagellum assembly context. Here we report that TbRP2 is required for the recruitment of T. brucei orthologs of MKS1 and MKS6, proteins that, in animal cells, are part of a complex that assembles at the base of the flagellum to regulate protein composition and cilium function. We also identify that TbRP2 is detected by YL1/2, an antibody classically used to detect α-tubulin. Together, these data suggest a general processing role for TbRP2 in trypanosome flagellum assembly and challenge the notion that TbRP2 functions solely in assessing tubulin "quality" prior to tubulin incorporation into the elongating axoneme.

Original languageEnglish
Pages (from-to)464-475
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number1
Early online date20 Nov 2013
DOIs
Publication statusPublished - 3 Jan 2014
Externally publishedYes

Fingerprint

Trypanosomiasis
Flagella
Tubulin
Axoneme
Basal Bodies
Trypanosoma brucei brucei
Proteins
Microtubule-Organizing Center
Animals
African Trypanosomiasis
Cytology
Cilia
Eukaryotic Cells
Microtubules
Cell Biology
Processing
Cells
Antibodies
Chemical analysis

Cite this

Andre, Jane ; Kerry, Louise ; Qi, Xin ; Hawkins, Erica ; Drižyte, Kristina ; Ginger, Michael L. ; McKean, Paul G. / An alternative model for the role of RP2 protein in flagellum assembly in the African trypanosome. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 1. pp. 464-475.
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An alternative model for the role of RP2 protein in flagellum assembly in the African trypanosome. / Andre, Jane; Kerry, Louise; Qi, Xin; Hawkins, Erica; Drižyte, Kristina; Ginger, Michael L.; McKean, Paul G.

In: Journal of Biological Chemistry, Vol. 289, No. 1, 03.01.2014, p. 464-475.

Research output: Contribution to journalArticle

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