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Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):E7341-E7350. doi: 10.1073/pnas.1805827115. Epub 2018 Jul 20.

Direction of flagellum beat propagation is controlled by proximal/distal outer dynein arm asymmetry.

Author information

1
Sir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, United Kingdom.
2
Sir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, United Kingdom; richard.wheeler@path.ox.ac.uk jsunter@brookes.ac.uk.
3
Department of Biological and Medical Sciences, Oxford Brookes University, OX3 0BP Oxford, United Kingdom richard.wheeler@path.ox.ac.uk jsunter@brookes.ac.uk.

Abstract

The 9 + 2 axoneme structure of the motile flagellum/cilium is an iconic, apparently symmetrical cellular structure. Recently, asymmetries along the length of motile flagella have been identified in a number of organisms, typically in the inner and outer dynein arms. Flagellum-beat waveforms are adapted for different functions. They may start either near the flagellar tip or near its base and may be symmetrical or asymmetrical. We hypothesized that proximal/distal asymmetry in the molecular composition of the axoneme may control the site of waveform initiation and the direction of waveform propagation. The unicellular eukaryotic pathogens Trypanosoma brucei and Leishmania mexicana often switch between tip-to-base and base-to-tip waveforms, making them ideal for analysis of this phenomenon. We show here that the proximal and distal portions of the flagellum contain distinct outer dynein arm docking-complex heterodimers. This proximal/distal asymmetry is produced and maintained through growth by a concentration gradient of the proximal docking complex, generated by intraflagellar transport. Furthermore, this asymmetry is involved in regulating whether a tip-to-base or base-to-tip beat occurs, which is linked to a calcium-dependent switch. Our data show that the mechanism for generating proximal/distal flagellar asymmetry can control waveform initiation and propagation direction.

KEYWORDS:

flagellum; intraflagellar transport; motility; outer dynein arm; trypanosomatid

PMID:
30030284
PMCID:
PMC6077732
[Available on 2019-01-31]
DOI:
10.1073/pnas.1805827115
[Indexed for MEDLINE]

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