The radial spokes and central apparatus: mechano-chemical transducers that regulate flagellar motility.

Abstract

The 9+2 microtubule arrangement is the most conserved axonemal configuration, suggesting that this organization has been retained under evolutionary pressure for crucial functions. The primary role of the nine outer doublet microtubules is well established: the associated dynein motors power the microtubule sliding that ultimately results in flagellar bending [Satir, 1968; Brokaw, 1972; Shingyoji et al., 1977]. In contrast, the role of the two central pair of microtubules (CP) and the radial spokes (RS) that project towards the CP is far less definitive. The CP/RS system appears to play an important role in motility of 9+2 axonemes since mutant organelles defective in either of these structural complexes are paralyzed [Witman et al., 1978; Sturgess and Chao, 1982; Neugebauer et al., 1990]. However, these mutant axonemes can be experimentally induced to beat using modified reactivation conditions [Frey et al., 1997; Wakabayashi et al., 1997; Yagi and Kamiya, 2000]. In addition, motility of naturally occurring central pairless cilia and flagella has been reported [Baccetti et al., 1979; Prensier et al., 1980; Nonaka et al., 1998]. Most notably, recent studies have demonstrated that the 9+0 nodal cilia of developing embryos are motile, and this motility plays a critical role in establishing left-right asymmetry [Nonaka et al., 1998; Marszalek et al., 1999; Nonaka et al., 2002]. These observations provide compelling evidence that the central apparatus and radial spokes are not absolutely required for oscillatory beating. What, then, is their function in cilia and flagella that possess the 9+2 arrangement of microtubules? Recent structural, biochemical, and functional studies have provided important new insights into these seemingly contradictory phenomena. Here, we review these findings and propose a model in which the central apparatus and radial spokes serve as mechano-chemical sensors to control motility in 9+2 cilia and flagella.