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Figure 1 | BMC Systems Biology

Figure 1

From: Computational modelling elucidates the mechanism of ciliary regulation in health and disease

Figure 1

Schematic diagram of the Ca2+-dependent regulation of motile cilium. (A) Schematic representation of the motile cilium movement trajectory for one complete beating cycle. The cycle is divided into two phases: effective stroke and recovery stroke shown by red and green arrows, respectively. The frequency and the direction of cilia movement is regulated in a highly complex Ca2+ and membrane voltage-mediated manner. (B) A typical cilium consists of an axoneme of nine doublet microtubules. The axoneme is surrounded by a specialized ciliary membrane that is separated from the cell membrane by a zone of transition fibres. This separation creates an intraciliary compartment where key regulatory events take place somewhat independently from the cell body. In particular, intraciliary Ca2+ concentration can significantly differ from intracellular levels. (C) The ciliary motion is regulated by intraciliary Ca2+ levels. The Ca2+ concentration depends on the interplay of ion channels and membrane potential, V m . The intraciliary Ca2+ concentration is dependent on currents via Ca2+, I C a 2 + I , and K+ channels, I K + , the system of active, I C a 2 + A , and passive, I C a 2 + p , ions removal, Ca2+ leakage current, I C a 2 + U , hyperpolarisation-activated currents I C a 2 + H T , inward current, I0, and the cilium-to-cell body current, I C a 2 + T . The conductivities of the channels are modulated by membrane potential. The result of the cross-talk between membrane potential and a variety of channels is that intraciliary Ca2+ can shift between several dynamic modes. The steady-state and dynamic Ca2+ alterations regulate the intraciliary levels of cAMP and cGMP in a Ca2+-CaM-dependent manner via the AC, GC and PDE isoforms [65]. Cyclic nucleotides, in turn, define the degree of phosphorylation of dynein filaments in the bases of ciliary axoneme via PKA and PKG kinases. Phosphorylation of dynein filaments regulates the relative doublet microtubules shift and thereby translates to the overall ciliary movement.

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