The single flagellum of Leishmania has a fixed polarisation of its asymmetric beat
Posted on: 6 April 2020
Preprint posted on 21 March 2020
Article now published in Journal of Cell Science at http://dx.doi.org/10.1242/jcs.246637
Deciphering what makes parasites tick: visualising swimming mechanisms of Leishmania parasites.
Selected by Mariana De NizCategories: biophysics, cell biology, microbiology
Background
Flagella and cilia are organelles that have essentially indistinguishable ultrastructures, but originally received different names based on their biological function, including their location within organisms, their structure, and their motion. Eukaryotic flagella undergo a beat that is symmetric planar near-sinusoidal, and there are few per cell. Conversely, eukaryotic cilia undergo an asymmetric planar wafting beat, and there are usually many per cell, undergoing coordinated motility within a tissue. Cilia/flagella have asymmetries which contribute to generating the correct beat form – firstly those which keep bending in a plane, and secondly those which introduce asymmetries in the beat with the correct polarisation.
Typical asymmetric beats undergo a power-stroke, which drives fluid movement relative to the cell, followed by a recovery stroke, returning the cilium/flagellum to its starting configuration. A planar asymmetric beat has two possible polarizations, corresponding to which way the power stroke pushes fluid as the flagellum beats. The single flagellum on Leishmania parasites undergoes a symmetric tip-to-base beat (typical of flagella) for forward swimming and an asymmetric base-to-tip beat (typical of cilia) to rotate the cell. An asymmetric beat can arise when a flagellum has a large static curvature (underlying shape of the flagellum) in addition to the symmetric dynamic curvature (the propagating wave). It is unknown whether a single Leishmania flagellum has a fixed polarization for its asymmetric beat.
Using a mixture of novel microscopy tools and genetic modification, in this preprint Wang et al (1) addressed this question, and investigated whether polarization is fixed or switchable, and the structures involved.
Key findings and developments
Main developments
- Wang et al developed high frame rate dual colour widefield epifluorescence of Leishmania parasites to observe the asymmetric internal cytoskeletal structure while also observing flagellum beatings.
- Wang et al generated various Leishmania mutants targeting different features of the flagellum and cell-flagellum attachment.
Main findings
- The authors showed that the flagellum has a fixed polarisation of the asymmetric flagellar beat.
- Paralysed flagellum mutants which form a static curvature (eg. deletion mutants for axonemal proteins, or extra-axonemal and rootlet-like flagellum-associated structures) retain a fixed polarisation.
- This asymmetry does not require the large paraflagellar rod structure or lateral attachment by the flagellum attachment zone.
- They hypothesize rather, that asymmetry is likely intrinsic to either the nine-fold rotational symmetry of the axoneme structure, or due to differences between the outer doublet decorations.
- These findings have important implications for understanding the mechanisms by which Leishmania achieves directed taxis.
Specific findings and developments (to know more details)
The asymmetric Leishmania beat occurs with a constant polarisation
- The dynamic curvature of both the tip-to-base and base-to-tip beats are near-symmetric, however the base-to-tip beats often do not propagate along the entire flagellum.
- While in other organisms ciliary beating is highly polarised, whether this is the case for Leishmania parasites was unknown. To determine a possible preferential direction, intracellular structures were used as reporters of cell orientation during flagellar beating -these included a flagellum membrane marker (SMP1) and a marker of the asymmetric microtubule-based cytoskeletal structure comprising the microtubule quartet and the lysosomal microtubule(s) (SPEF1).
- The latter allows inferring the orientation of the flagellum axoneme, paraflagellar rod, and flagellar attachment zone.
The paraflagellar rod is on the inside of the tightly curved recovery stroke
- The paraflagellar rod sits on the leading side of the flagellum during the asymmetric beat power stroke which corresponds to the inside of the static curvature. The paraflagellar rod was consistently offset from the axoneme.
- The authors concluded that the paraflagellar rod experiences greater compression during the recovery stroke/reverse bend than extension during the power stroke/principal bend.
Mutants only able to form a static bend have inverted polarization to asymmetric beats.
- In Leishmania, deletion mutants of many conserved axoneme proteins have a paralysed flagellum, and are unable to undergo a beat because they lack the dynamic bending component. In a subset of these, the paralysed flagella retain some capacity for bending and have a curled configuration. These mutants can form a static but not a dynamic flagellar beat.
- The authors tested whether the static curvature of some of these mutants retains a preferred polarisation. The curved flagella in two mutants (for inner dynein arms, and central pairs) had a preferred bend direction towards the side of the cell with the lysosomal microtubule with the paraflagellar rod on the outside of the coil. The curvature was also much larger than in WT parasites.
Disruption of asymmetric extra-axonemal flagellum structures does not alter polarisation
- PFR2 is a major structural component of the paraflagellar rod and its deletion leads to loss of almost all of the paraflagellar rod.
- In Leishmania this leads to a flagellar beat which is still dominantly tip-to-base but with a shorter wavelength and lower amplitude, leading to slower forward swimming.
- The authors found that the tip-to-base beat was still near-symmetrical, while the more infrequent base-to-tip beat was asymmetric with normal polarity, albeit with less pronounced asymmetry than in WT parasites.
- FAZ5 is vital for lateral attachment between the flagellum and the flagellar pocket neck. Its loss results in a motility defect. The authors determined whether this defect was due to altered asymmetry of the base-to-tip beat.
- Almost all flagella underwent a base-to-tip beat, suggesting a reduced ability for a tip-to-base beat is the origin of the previously observed swimming defect.
- The base-to-tip beats appeared normal and consistently occurred with normal polarization.
What I like about this preprint
My main interests are biophysics and its use to understand parasitology. This preprint focuses precisely on this, and carefully dissects a topic that might be key to understand parasite behaviour, including pathology in hosts. Moreover, the authors designed various tools that made this work possible.
References
- Wang et al, The single flagellum of Leishmania has a fixed polarisation of its asymmetric beat, 2020, bioRxiv, doi: 10.1101/2020.03.21.001610
doi: https://doi.org/10.1242/prelights.18159
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