I1/f dynein and the nexin–dynein regulatory complex form two hubs to control dynein activity and ciliary beating

Ciliary motility is critical for the development and health of many organisms. Motility depends on the selective activation and inhibition of the multiple dynein motors along the length and around the circumference of the ciliary axoneme. This chapter focuses on two molecular hubs that are located near the base of the radial spokes (RS) and regulate dynein activity in the axoneme. The first radial spoke (RS1) is associated with inner arm dynein known as I1/f or f dynein. I1/f dynein is attached to the outer doublet microtubule using an intermediate-chain/light-chain (IC/LC) complex at its base and a tether head complex at its motor domains. The I1/f IC/LC complex is also linked to the modifier of inner arm complex. The second radial spoke (RS2) is associated with a calmodulin spoke complex and the nexin–dynein regulatory complex (N-DRC). Nexin was first identified as an interdoublet linker that repeats every 96nm along the length of the axoneme and was proposed to limit microtubule sliding and thus generate bending during the ciliary beat cycle. The N-DRC is also thought to be a regulator in the signaling pathway between the central apparatus, RS, and dynein arms. Recent high-resolution structural and proteomic studies have provided new insights into the composition, organization, and three-dimensional structure of these regulatory hubs. The implications of these findings for the regulation of ciliary motility are discussed in this chapter.