Eukaryotic cilia and flagella are highly conserved, microtubule-based structures that play fundamental roles in sensory transduction and cell motility. This chapter focuses on the dynein regulatory complex (DRC), about which very little is known so far. It begins with a brief review of the work on the central-pair microtubules and radial spokes, which are required for flagellar motility in Chlamydomonas under physiological conditions. Following this, it deals with the identification and characterization of two groups of extragenic suppressor mutations that can restore motility to paralyzed central pair/radial spoke defective mutants. The first group of suppressor mutations has demonstrated that specific changes in both the outer and inner dynein arms can override defects in the central-pair/radial-spoke complex to restore motility. Characterization of the second group of suppressors, the DRC mutants, has revealed that the DRC serves both as an adaptor for the binding of specific inner-arm dynein isoforms and as part of the nexin link that resists microtubule sliding. It also reviews the recent efforts to identify nexine DRC subunits and localizes them within the substructure of the DRC. Finally, it presents the proposed functions of the DRC and nexin links and discusses possible future directions for research.
|Original language||English (US)|
|Title of host publication||Dyneins|
|Number of pages||30|
|State||Published - 2012|
Bibliographical noteFunding Information:
Many thanks to the past and present members of my laboratory for their hard work and dedication to our studies on flagellar dynein and its regulation. I am also grateful to many wonderful collaborators over the years, including Susan Dutcher, David Mitchell, Dick Linck, Winfield Sale, and Maureen Wirschell. A special thanks to my collaborators at the Boulder Laboratory for 3D Fine Structure, David Mastronarde, Eileen O’Toole, and Dick McIntosh, for their tireless efforts to push the envelope and see new details of axoneme structure, and to Thomas Heuser and Daniela Nicastro at Brandeis University, who have now brought our studies into a third dimension. Our work is supported by a grant (GM55667) from the National Institutes of Health.