A family of co-chaperones helps preassemble dynein motor complexes in the cytoplasm before they move into cilia and flagella, Yamamoto et al. report.
Cilia movements are powered by dynein arms that connect neighboring outer microtubule doublets in the organelle's axoneme. Rather than separately transporting individual dynein subunits into the flagellum, each motor complex is preassembled in the cytoplasm before moving into position. The flagella of Chlamydomonas contain eight different dynein arms, some of which are preassembled with the help of a co-chaperone called PF13. Yamamoto et al. found that a related protein, MOT48, is mutated in a Chlamydomonas strain with motility defects and reduced levels of axonemal dyneins.
Inner arm dyneins b, c, and d were particularly decreased in MOT48's absence, a distinct but overlapping set of dyneins compared to those affected by the loss of PF13. Dynein protein levels were decreased in the cytoplasm as well as the flagella of mutant algae—the co-chaperones may help dynein heavy chains fold and stabilize the subunits as they assemble into a transport-ready complex.
Both PF13 and MOT48 contain a PIH domain, originally described in a budding yeast protein that interacts with the chaperone Hsp90. Yamamoto et al. identified a third PIH protein in Chlamydomonas called TWI1, whose homologue in zebrafish is also required for cilia motility. Senior author Ritsu Kamiya now plans to investigate whether TWI1 assembles the flagellar dyneins not covered by either PF13 or MOT48. He also wants to explore whether—like PF13—MOT48 helps build axonemal dyneins in higher eukaryotes as well.