Calcium Signaling in Flagella

Abstract

Ciliary and flagellar movement is powered by an axoneme structure composed of a central pair of microtubules that is surrounded by nine microtubule doublets. Dynein motors control the force-generating sliding of microtubules against each other, and radial spokes of the axoneme control the bending motion. This machinery is thought to be controlled, in part, by calcium. Although calcium-binding proteins have been identified in flagella, their connections to specific signaling pathways have remained obscure. Patel-King et al . have identified a nucleoside diphosphate kinase (NDKase; p61/RSP23) in the Chlamydomonas flagellum that is tightly associated with radial spokes. NDKases preferentially catalyze the generation of guanosine triphosphate (GTP). The protein was not detected in a mutant strain lacking radial spoke stalks, suggesting a specific location within the axoneme. In sucrose gradient analysis of flagellar extracts, p61 cofractionated with other radial spoke proteins and with peak NDKase activity. The kinase contains three motifs that bind to calmodulin in vitro, two of which mediate calcium-dependent interactions. Earlier pharmacological studies suggested the presence of calmodulin in the radial spoke. The authors suggest that in response to a calcium signal, GTP is produced in the radial stalk. Local increases in GTP could affect GTP-binding proteins present in the axoneme that could transduce this signal. Alternatively, GTP could be converted to cGMP, which could also modulate other components of the radial spoke. These signals could ultimately be transmitted to dynein motors for the control of microtubule sliding. R. S. Patel-King, O. Gorbatyuk, S. Takebe, S. M. King, Flagellar radial spokes contain a Ca 2+ -stimulated nucleoside diphosphate kinase. Mol. Biol. Cell 15 , 3891-3902 (2004). [Abstract] [Full Text]