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Stuck in reverse: loss of LC1 in Trypanosoma brucei disrupts outer dynein arms and leads to reverse flagellar beat and backward movement.

Abstract：

:Axonemal dyneins are multisubunit molecular motors that provide the driving force for flagellar motility. Dynein light chain 1 (LC1) has been well studied in Chlamydomonas reinhardtii and is unique among all dynein components as the only protein known to bind directly to the catalytic motor domain of the dynein heavy chain. However, the role of LC1 in dynein assembly and/or function is unknown because no mutants have previously been available. We identified an LC1 homologue (TbLC1) in Trypanosoma brucei and have investigated its role in trypanosome flagellar motility using epitope tagging and RNAi studies. TbLC1 is localized along the length of the flagellum and partitions between the axoneme and soluble fractions following detergent and salt extraction. RNAi silencing of TbLC1 gene expression results in the complete loss of the dominant tip-to-base beat that is a hallmark of trypanosome flagellar motility and the concomitant emergence of a sustained reverse beat that propagates base-to-tip and drives cell movement in reverse. Ultrastructure analysis revealed that outer arm dyneins are disrupted in TbLC1 mutants. Therefore LC1 is required for stable dynein assembly and forward motility in T. brucei. Our work provides the first functional analysis of LC1 in any organism. Together with the recent findings in T. brucei DNAI1 mutants [Branche et al. (2006). Conserved and specific functions of axoneme components in trypanosome motility. J. Cell Sci. 119, 3443-3455], our data indicate functionally specialized roles for outer arm dyneins in T. brucei and C. reinhardtii. Understanding these differences will provide a more robust description of the fundamental mechanisms underlying flagellar motility and will aid efforts to exploit the trypanosome flagellum as a drug target.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Baron DM,Kabututu ZP,Hill KL

doi

10.1242/jcs.004846

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

1513-20

issue

Pt 9

eissn

0021-9533

issn

1477-9137

pii

jcs.004846

journal_volume

120

pub_type

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Stuck in reverse: loss of LC1 in Trypanosoma brucei disrupts outer dynein arms and leads to reverse flagellar beat and backward movement.