Figure 9.

Possible ways ARL13B could contribute to HNN cell migration phenotype. See text for details. 1. The stunted HNN cilium impairs sensing of extracellular gradients. It senses PDGF, SHH, WNT and might contribute to sensing of EGF; some of these pathways are important in DCEF migration. 2. Diminished ERK phosphorylation contributes to poor polarization of the Golgi apparatus and centrosome, which is necessary for cell migration. 3. Dysfunctional centrosome docking and release during migration. This would determine a 'migrate/don't migrate' decision because the centrosome can't simultaneously support the primary cilium and migration. 4. ARL13B co-localizes at the leading edge with CDC42, which has been shown previously to control DCEF migration. Additionally, it is enriched also in actin rich structures present on the leading edge of the cell. 5. Aberrant ARL13B GTPase activity further contributes to a more stable, less motile microtubule cytoskeleton.