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, 2018) 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.

Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule

“…Axonemal dyneins drive ciliary bending (King, 2018; Satir et al, 2014). Most models suggest that localized activation and inhibition of axonemal dyneins is needed to create the imbalance in forces across the axoneme that result in an overall bend.…”

CCB is Involved in Actin-Based Axonal Transport of Selected Synaptic Proteins

“…Two main transport systems are known based on the supporting cytoskeletal network: (1) a high-speed, long-range microtubulebased system; and (2) a slow-speed, local-range actin-based system. Microtubule-based transport uses motor proteins of the kinesin and dynein families binding to the plus (anterograde) and minus (retrograde) end of microtubules, respectively (Hirokawa et al, 2010;King, 2018). Myosin is the corresponding motor protein along actin filaments.…”

Calaxin is essential for the transmission of Ca2+-dependent asymmetric waves in sperm flagella

“…In particular, local sliding between doublet microtubules by dyneins is essential for bend formation (Shingyoji et al, 1977). Indeed, coordinated activation or inactivation of dyneins within nine sets of doublet microtubules along the flagella controls the bend curvature, bending direction, wavelength, and propagation velocity (Inaba, 2011, Lin and Nicastro, 2018, King, 2018. For instance, switching of dynein activity between doublet 7 and 3 is thought to be responsible for the periodical and planar oscillation of sperm flagella.…”