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Review
. 2017 Aug 1;9(8):a018325.
doi: 10.1101/cshperspect.a018325.

Ciliary Motility: Regulation of Axonemal Dynein Motors

Rasagnya Viswanadha  1 , Winfield S Sale  1 , Mary E Porter  2
Affiliations
Review

Ciliary Motility: Regulation of Axonemal Dynein Motors

Rasagnya Viswanadha et al. Cold Spring Harb Perspect Biol. .

Abstract

Ciliary motility is crucial for the development and health of many organisms. Motility depends on the coordinated activity of multiple dynein motors arranged in a precise pattern on the outer doublet microtubules. Although significant progress has been made in elucidating the composition and organization of the dyneins, a comprehensive understanding of dynein regulation is lacking. Here, we focus on two conserved signaling complexes located at the base of the radial spokes. These include the I1/f inner dynein arm associated with radial spoke 1 and the calmodulin- and spoke-associated complex and the nexin-dynein regulatory complex associated with radial spoke 2. Current research is focused on understanding how these two axonemal hubs coordinate and regulate the dynein motors and ciliary motility.

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Figures

Figure 1.
Figure 1.
Cross section of the axoneme and illustration of the “switching model” for alternating forward and reverse bends. The 9 + 2 structure comprises nine outer doublet microtubules and a pair of singlet microtubules, C1 and C2, collectively known as the central pair. The outer doublet anchors the outer dynein arms (ODA), the radial spokes (RS), and the inner dynein arms, including I1 dynein. The black line passing through doublet #6 and between doublets #1 and #2 represents the plane/axis of bending. According to the switching model, when dyneins on one side of the axis are active (i.e., on doublets #2, #3, and #4), microtubule sliding can result in the forward, or effective, bend (green in inset). When the direction of bending reverses, the dyneins on doublets #2, #3, and #4 are inactivated, and dyneins on doublets #6, #7, and #8 are switched on to generate the recovery, or reverse, bend (blue in inset). (Adapted, with permission, from Smith 2007, © Journal of Cell Biology.)
Figure 2.
Figure 2.
Parallel control pathways associated with the two regulatory hubs present in the 96-nm repeat: (1) RS1 and I1 dynein–MIA complex, and (2) RS2, CSC, and N-DRC. The blue arrows indicate chemical and mechanical signals that emanate from the central pair (CP) projections and are transmitted through the radial spoke heads to the bases of RS1 and RS2. The red arrows indicate signals transmitted from RS1 to the I1 dynein-MIA complex and from RS2 to the CSC and N-DRC, respectively, to control ciliary motility. The outer dynein arms (ODA) are also connected to both the I1–MIA complex and the N-DRC, also shown by the red arrows. CSC, calmodulin- and spoke-associated complex; N-DRC, nexin–dynein regulatory complex; IC, intermediate chain; LC, light chain; MIA, modifier of inner arms; RS, radial spoke. (Adapted from Yamamoto et al. 2013; King 2013.)
Figure 3.
Figure 3.
Diagram of interactions within I1 dynein and with the MIA complex and associated proteins. As illustrated in the inset, I1 dynein contains two distinct heavy chain motor domains (HC1α and HC1β), three intermediate chains (IC140, IC97, and IC138), and five light chains (Tctex1, Tctex2b, LC8, LC7a, and LC7b). The solid lines represent protein–protein interactions determined by biochemical and/or structural analysis of I1 dynein assembly mutants (1: Myster et al. 1997; 2: Perrone et al. 2000; 3: Bower et al. 2009; 4: Toba et al. 2011; 5: VanderWaal et al. 2011; 6: Perrone et al. 1998; 8: Wirschell et al. 2009; 9: Hendrickson et al. 2004; 11: DiBella et al. 2004a; 16: Yamamoto et al. 2013). The dashed lines indicate predicted interactions based on the analysis of I1 assembly mutants (6: Perrone et al. 1998; 7: Heuser et al. 2012a; 10: Ikeda et al. 2009; 11: DiBella et al. 2004a; 12: Viswanadha et al. 2014; 13: Wu et al. 2005; 14: Harrison et al. 1998; 15: Yang et al. 2009; 16: DiBella et al. 2004b). (Adapted from DiBella et al. 2004a; King 2013.)
Figure 4.
Figure 4.
The Chlamydomonas axoneme ultrastructure. (A–C). Cryo-electron tomography slices show (A) a longitudinal view, (B) a 3D view, and (C) a cross section of a Chlamydomonas axoneme. The red boxes highlight one 96-nm axonemal repeat unit in both views. (D,E) Isosurface renderings show an averaged 96-nm axonemal repeat in (D) longitudinal and (E) cross-sectional orientation. The cross-sectional slice is taken close to radial spoke 2, viewing from the proximal to the distal end. Key axonemal structures are highlighted: A- and B-tubule (At,Bt), nexin–dynein regulatory complex (N-DRC), radial spokes (RS1,RS2), calmodulin- and spoke-associated complex (CSC), and inner and outer dynein arms (IA,OA). Inner-arm dyneins include the I1 complex (dynein f α and β heavy chain motor domains) and dyneins a–g. (Adapted from Satir et al. 2014; originally from Heuser et al. 2012b, with permission of the American Society for Cell Biology; permission conveyed through Copyright Clearance Center, Inc.; Heuser et al. 2012a.)
Figure 5.
Figure 5.
Cryo-electron tomography (cryo-ET) reconstruction of the nexin–dynein regulatory complex (N-DRC). This image shows the N-DRC in yellow, as viewed from the distal end of a 96-nm axoneme repeat in cross section. A single outer doublet is shown here, with a subset of protofilaments numbered in the A tubule (At) and B tubule (Bt). The outer dynein arms (ODA) are shown in gray at the top left, and one of the inner dynein arms (IDA) is shown in gray at the bottom left. The baseplate of the N-DRC is attached to protofilament 11 on the B tubule and wraps around the underside of the A tubule until protofilament 4. The linker of the N-DRC extends from the surface of the A tubule toward the neighboring outer doublet, and it also contacts both the IDA (at L1) and the ODA (red arrowhead). Radial spoke 2 (RS2) attaches to the A tubule just behind the N-DRC. The calmodulin- and spoke-associated complex (CSC) sits at the base of RS2 and wraps around the N-DRC to the next RS3 or RS3S, which is not shown here. The precise boundaries among the subunits of RS2, the CSC, and the base of the DRC are not well defined. (Adapted from Heuser et al. 2009.)
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