Integrated regulatory axes controlling dynein motors in the ciliary axoneme

The motile cilium is a highly conserved and stunningly complex machine involved in the movement of individual cells and organisms and the generation of fluid flow. Ciliary beating is driven by arrays of dynein motors acting on doublet microtubules. These multi-component enzymes are built around the heavy chain motor units, contain a variety of associated structural and regulatory proteins, and can have masses approaching 2 MDa. The beat parameters of these organelles are subject to numerous signaling inputs that control motor function and waveform kinematics. Interactions both within individual dyneins and between adjacent dyneins are important for regions of dynein activity to travel along the cilium. Dyneins respond to mechanical feedback and the imposition of viscous load, changes in the ciliary redox state and Ca 2+ levels, and in some organisms even have a dedicated blue light sensor. These enzymes are also subject to numerous, often sub-stoichiometric, post-translational modifications including phosphorylation, methylation and N-terminal acetylation that can impact assembly and motor properties. Here we review advances in the study of dynein regulatory mechanisms and examine how these differing and tunable inputs are integrated to yield motile behaviors that rapidly respond to changes in environmental conditions.