Compartmentalized Calcium Signaling in Cilia Regulates Intraflagellar Transport

Abstract

Intraflagellar transport (IFT) underpins many of the important cellular roles of cilia and flagella in signaling and motility. The microtubule motors kinesin-2 and cytoplasmic dynein 1b drive IFT particles (protein complexes carrying ciliary component proteins) along the axoneme to facilitate the assembly and maintenance of cilia. IFT is regulated primarily by cargo loading onto the IFT particles, although evidence suggests that IFT particles also exhibit differential rates of movement. Here we demonstrate that intraflagellar Ca(2+) elevations act to directly regulate the movement of IFT particles. IFT-driven movement of adherent flagella membrane glycoproteins in the model alga Chlamydomonas enables flagella-mediated gliding motility. We find that surface contact promotes the localized accumulation of IFT particles in Chlamydomonas flagella. Highly compartmentalized intraflagellar Ca(2+) elevations initiate retrograde transport of paused IFT particles to modulate their accumulation. Gliding motility induces mechanosensitive intraflagellar Ca(2+) elevations in trailing (dragging) flagella only, acting to specifically clear the accumulated microtubule motors from individual flagella and prevent a futile tug-of-war. Our results demonstrate that compartmentalized intraciliary Ca(2+) signaling can regulate the movement of IFT particles and is therefore likely to play a central role in directing the movement and distribution of many ciliary proteins.