Axonemal dynein contributions to flagellar beat types and waveforms

Area of Science:

• Cell Biology
• Biophysics
• Molecular Motors

Background:

• Eukaryotic flagella (motile cilia) are crucial for cell propulsion and fluid transport.
• Dysfunctional flagellar beating leads to human diseases like ciliopathies and infertility.
• The precise mechanism by which different dynein motor proteins generate diverse flagellar beat types remains largely unknown.

Purpose of the Study:

• To elucidate the functional division of labor among dynein motor proteins in generating specific flagellar beat types.
• To investigate the role of different dynein complexes in the flagellar beat waveform and incidence.
• To challenge and refine existing models of flagellar motility control.

Main Methods:

• Utilized cryo-electron microscopy (cryo-EM) to determine the structure of the flagellar 96-nm repeat unit.
• Employed CRISPR-Cas9 gene editing to systematically delete 96-nm repeat proteins in *Leishmania*.
• Analyzed the impact of these deletions on flagellar swimming, beat incidence, and waveform.

Main Results:

• Identified the dynein composition of the flagellar 96-nm repeat unit.
• Demonstrated that outer dynein arms (ODAs) are essential for symmetric tip-to-base beats.
• Showed that specific inner dynein arms (IDAs), namely IDA*d* and IDA*f*, are critical for asymmetric base-to-tip beats and overall waveform modulation.

Conclusions:

• Established a division of labor where distinct dyneins are responsible for specific flagellar beat types.
• Provided evidence that challenges the universal dogma of ODAs driving and IDAs shaping flagellar beats.
• Proposed new hypotheses for the regulation of flagellar beat diversity across different cell types and organisms.