Turning dyneins off bends cilia.

Abstract

Ciliary and flagellar motility is caused by the ensemble action of inner and outer dynein arm motors acting on axonemal doublet microtubules. The switch point or switching hypothesis, for which much experimental and computational evidence exists, requires that dyneins on only one side of the axoneme are actively working during bending, and that this active motor region propagate along the axonemal length. Generation of a reverse bend results from switching active sliding to the opposite side of the axoneme. However, the mechanochemical states of individual dynein arms within both straight and curved regions and how these change during beating has until now eluded experimental observation. Recently, Lin and Nicastro used high‐resolution cryo‐electron tomography to determine the power stroke state of dyneins along flagella of sea urchin sperm that were rapidly frozen while actively beating. The results reveal that axonemal dyneins are generally in a pre‐power stroke conformation that is thought to yield a force‐balanced state in straight regions; inhibition of this conformational state and microtubule release on specific doublets may then lead to a force imbalance across the axoneme allowing for microtubule sliding and consequently the initiation and formation of a ciliary bend. Propagation of this inhibitory signal from base‐to‐tip and switching the microtubule doublet subsets that are inhibited is proposed to result in oscillatory motion.