The roles of a flagellar HSP40 ensuring rhythmic beating

X Zhu, E Poghosyan, L Rezabkova… - Molecular biology of …, 2019 - Am Soc Cell Biol
X Zhu, E Poghosyan, L Rezabkova, B Mehall, H Sakakibara, M Hirono, R Kamiya…
Molecular biology of the cell, 2019Am Soc Cell Biol
HSP40s are regarded as cochaperones, perpetually shuttling client polypeptides to HSP70s
for refolding. However, many HSP40s that are central for disparate processes diverge from
this paradigm. To elucidate the noncanonical mechanisms, we investigated HSP40 in the
radial spoke (RS) complex in flagella. Disruption of the gene by the MRC1 transposon in
Chlamydomonas resulted in jerky flagella. Traditional electron microscopy, cryo-electron
tomography, and sub-tomogram analysis revealed RSs of various altered morphologies that …
HSP40s are regarded as cochaperones, perpetually shuttling client polypeptides to HSP70s for refolding. However, many HSP40s that are central for disparate processes diverge from this paradigm. To elucidate the noncanonical mechanisms, we investigated HSP40 in the radial spoke (RS) complex in flagella. Disruption of the gene by the MRC1 transposon in Chlamydomonas resulted in jerky flagella. Traditional electron microscopy, cryo-electron tomography, and sub-tomogram analysis revealed RSs of various altered morphologies that, unexpectedly, differed between the two RS species. This indicates that HSP40 locks the RS into a functionally rigid conformation, facilitating its interactions with the adjacent central pair apparatus for transducing locally varied mechanical feedback, which permits rhythmic beating. Missing HSP40, like missing RSs, could be restored in a tip-to-base direction when HSP40 mutants fused with a HSP40 donor cell. However, without concomitant de novo RS assembly, the repair was exceedingly slow, suggesting HSP40/RS-coupled intraflagellar trafficking and assembly. Biochemical analysis and modeling uncovered spoke HSP40’s cochaperone traits. On the basis of our data, we propose that HSP40 accompanies its client RS precursor when traveling to the flagellar tip. Upon arrival, both refold in concert to assemble into the mature configuration. HSP40’s roles in chaperoning and structural maintenance shed new light on its versatility and flagellar biology.
Am Soc Cell Biol
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