Regulation of mammalian ciliary beating

Recent advances in our understanding of the structure-function relationship of motile cilia with the 9 + 2 microtubular arrangement have helped explain some of the mechanisms of ciliary beat regulation by intracellular second messengers. These second tnessengers include cyclic adenosine monophosphate (CAMP) and cyclic guanosine tnonophosphate (cGMP) as well as calcium and pH. cAMP activates protein kinase A (PKA), which is localized to the axoneme. The CAMP-dependent phosphorylation of PKA's main target, originally described as p29 in Paramecium, seems to increase eiliary beat frequency (CBF) directly. The mechanism by which eGMP increases CBF is less well defined but involves protein kinase G and possibly PKA. Protein kinase C inhibits ciliary beating. The regulation mechanisms of CBF by calcium remain somewhat controversial, favoring an immediate, direct action of calcium on ciliary beating and a second cyclic nucleotide-dependent phase. Finally, intracellular pH likely affects CBF through direct influences on dynein arms.