REGULATION OF FLAGELLAR DYNEIN BY PHOSPHORYLATION OF A 138-KD INNER ARM DYNEIN INTERMEDIATE CHAIN

One of the challenges in understanding ciliary and flagellar motility is determining the mechanisms that locally regulate dynein-driven micr otubule sliding. Our recent studies demonstrated that microtubule slid ing, in Chlamydomonas flagella, is regulated by phosphorylation. Howev er, the regulatory proteins remain unknown. Here we identify the 138-k D intermediate chain of inner arm dynein Il as the critical phosphopro tein required for regulation of motility. This conclusion is founded o n the results of three different experimental approaches. First, genet ic analysis and functional assays revealed that regulation of microtub ule sliding, by phosphorylation, requires inner arm dynein I1. Second, in vitro phosphorylation indicated the 138-kD intermediate chain of I 1 is the only phosphorylated subunit. Third, in vitro reconstitution d emonstrated that phosphorylation and dephosphorylation of the 138-kD i ntermediate chain inhibits and restores wild-type microtubule sliding, respectively. We conclude that change in phosphorylation of the 138-k D intermediate chain of I1 regulates dynein-driven microtubule sliding . Moreover, based on these and other data, we predict that regulation of I1 activity is involved in modulation of flagellar waveform.