The 9 + 2 Axoneme Anchors Multiple Inner Arm Dyneins and a Network of Kinases and Phosphatases That Control Motility

Cilia and flagella are found on a variety of cell types, ranging from single cell protozoa and sperm to the ciliated epithelia of the respiratory and reproductive tracts.Despite this diversity, most motile cilia and flagella contain a highly ordered structure, the 9 ϩ 2 axoneme (Fig. 1 A), which is composed of Ͼ 250 distinct, but well conserved polypeptides (Luck, 1984).Ciliary motility is generated by the dynein-driven sliding of outer doublet microtubules.Defects in the dynein motors or components that regulate their activity can have profound consequences; in vertebrates, these include infertility, respiratory disease, and defects in the determination of the left-right axis during embryonic development (Afzelius, 1999;Supp et al., 2000).The biochemical complexity of the organelle has made it challenging to identify the relevant loci by traditional mapping methods (Blouin et al., 2000).However, significant progress is being made using candidate genes identified in model organisms.For instance, it is much simpler to analyze mutations affecting flagellar motility in Chlamydomonas using biochemical, structural, and molecular approaches (Fig. 1 A ;Dutcher, 1995;Mitchell, 2000), and then identify related genes with similar functions in other species (Neilson et al., 1999;Pennarun et al., 1999).In this review, we discuss recent findings, primarily in Chlamydomonas , that are providing new insights into the regulation of dynein-based motility within the axoneme.The inner arms, which are both necessary and sufficient to generate flagellar bends, determine the size and shape of the waveform; the outer dynein arms add power and increase beat frequency approximately twofold (Brokaw and Kamiya, 1987).As the structure and regulation of the outer dynein arms recently have been reviewed (Satir, 1998;King, 2000), we focus here on components that control inner arm activity through structural interactions and enzymatic phosphorylation.We first review the evidence that each inner arm dynein plays a distinct role in the generation and control of motility, and that the central pair apparatus and radial spokes (CP/RS) 1 interact with the inner arms to control the flagellar waveform.We then discuss new evidence for a network of enzymes closely associated with the CP/RS complex that may locally modulate inner arm activity to regulate motility.