Function of TRIP6 in brain-specific ciliogenesis

Ciliogenesis is a multi-step multi-component process, the disruption of which results in developmental or homeostasis-relevant diseases. In common with assembly of other multiprotein complexes, ciliogenesis may be facilitated by molecular scaffold and assembly factors. The zyxin family of LIM domain proteins, including TRIP6, exert scaffolding functions, e.g. in cellular adhesion. trip6 deletion in the mouse revealed, unexpectedly, in view of its ubiquitous expression, a brain-specific function: ependymal and choroid plexus epithelial cells were poorly developed, carrying fewer and shorter cilia, and the mice developed hydrocephalus. Super-resolution microscopy demonstrated TRIP6 localization at the pericentriolar material and along the axoneme (co-localizing with ARL13B and CLUAP1) suggestive of a co-transporter function. Disruption of TRIP6, via RNAi or inhibition of its dimerization, in a choroid plexus cell line confirmed its function in ciliogenesis. The requirement for dimerization, which doubles its interaction sites, suggests an additional scaffold function for TRIP6 at the cilium. In conclusion, our data demonstrates a new function of TRIP6 in brain ciliogenesis.