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Figure 16 | BMC Systems Biology

Figure 16

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

Figure 16

Systems model for ciliary excitation offers new avenues for mechanistic interpretation of ciliary pathologies. The systems model for intraciliary Ca2+ regulation offers new strategies for interpretation of experimental data and development of pharmaceutical interventions for ciliary motility-associated pathologies. The ciliary system is predicted to maintain either low (A) or high (B) levels of intraciliary Ca2+. The extracellular conditions can shift the functional modes of ciliary activity and cause a temporal, repetitive or a long term Ca2+ increase which causes cilia to reverse the direction of beat. The long term reversal of the direction of beat can explain the mechanism of the situs inversus disease, which is a congenital condition in which the major organs are mirrored with respect to their normal positions. Intraciliary Ca2+ levels modulate ciliary beat frequency [65] via either an external signal through the G-protein mediated pathways or by parametric regulation of GC activity. Such alterations can represent a physiological response to external and intracellular signals, but can also occur as a result of genetic mutations. According to our model, the latter case represents a potential pathology and in either case of permanent Ca2+-dependent CBF alteration (C or D) requires the development of therapeutic strategies to rescue the mutation-mediated alteration of the system.

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