A simplified signalling schematic to show proposed events where the cilium is proposed to regulate (highlighted in red). In the absence of IL-1, IκB traps p65 in the cytoplasm. In the presence of IL-1, receptor related events lead to the activation (phosphorylation as denoted by small black p) of IKK. These events are not dependent upon the ciliary compartment, as indicated by data in Fig. 3. However, the primary cilium may represent a critical location for, even scaffold upon which, the key molecular interactions between activated IKK and IκB, leading to IκB destruction, take place (as indicated by the data in Fig. 4). These events allow NFκB p65 release to the nucleus and are mistimed or diminished in magnitude without the cilium (as indicated by the data in Fig. 2). Ciliary trafficking of IKK and IκB to interact with ciliary hsp27 (Fig. 5) may allow controlled and rapid phosphorylation of IκB and its subsequent destruction, releasing a burst of p65 transcription factor to bind to transcriptional targets such as iNOS and COX2. In the absence of functional IFT88 cilia trafficking (ORPK) the delay or reduction in magnitude of these events results in a failure to induce target (Fig. 1).
Wann AK, Chapple JP, Knight MM. The primary cilium influences interleukin-1β-induced NFκB signalling by regulating IKK activity. Cell Signal. 2014 Aug;26(8):1735-42.
He Z, Leong DJ, Zhuo Z, Majeska RJ, Cardoso L, Spray DC, Goldring MB, Cobelli NJ, Sun HB. Strain-induced mechanotransduction through primary cilia, extracellular ATP, purinergic calcium signaling, and ERK1/2 transactivates CITED2 and downregulates MMP-1 and MMP-13 gene expression in chondrocytes. Osteoarthritis Cartilage. 2016 May;24(5):892-901
