Integrated control of axonemal dynein AAA(+) motors

Abstract

Axonemal dyneins are AAA(+) enzymes that convert ATP hydrolysis to mechanical work. This leads to the sliding of doublet microtubules with respect to each other and ultimately the generation of ciliary/flagellar beating. However, in order for useful work to be generated, the action of individual dynein motors must be precisely controlled. In addition, cells modulate the motility of these organelles through a variety of second messenger systems and these signals too must be integrated by the dynein motors to yield an appropriate output. This review describes the current status of efforts to understand dynein control mechanisms and their connectivity focusing mainly on studies of the outer dynein arm from axonemes of the unicellular biflagellate green alga Chlamydomonas.

Figure 1. Composition and Organization of Outer Arm Dynein

The composition and organization of the Chlamydomonas outer dynein arm is diagramed. This complex enzyme is built around three AAA⁺ motors (α, β, and γ) which associate directly with a series of LCs (LCs 1, 3, 4, 5) that transduce mechanical, Ca²⁺ and redox signals. The HCs in turn associate with a complex consisting of two WD-repeat ICs which contain N-terminal regions to which a series of LCs (LCs2, 6, 7a, 7b, 8 and 10) bind. One of these LCs (LC7a) interacts with a component of the trimeric docking complex that anchors the structure within the axoneme. The ODA5 protein is also required for assembly but its associations are uncertain (Wirschell et al., 2004). Finally, the ODA7 protein may mediate association of the outer arm with inner arm I1/f (Freshour et al., 2007).

Figure 2. Integrated Signaling Pathway for Outer Arm Dynein

This diagram illustrates the known signals that impinge on Chlamydomonas outer arm dynein (green), the effector molecules (pink), the distinct HC motor components (light blue) and the functional output (yellow/red). Of note is that each HC acts to integrate a distinct set of signals: redox, Lis1 and phosphorylation (α HC), redox (β HC), and Ca²⁺, mechanical sensing, phosphorylation, and redox state (γ HC). The lack of individual motor units also leads to distinct phenotypic results which likely derive from both alterations in motor function and disruption of particular signaling modalities.