Abstract
TRIP6, a member of the ZYXIN-family of LIM domain proteins, is a focal adhesion component. Trip6 deletion in the mouse, reported here, reveals a function in the brain: ependymal and choroid plexus epithelial cells are carrying, unexpectedly, fewer and shorter cilia, are poorly differentiated, and the mice develop hydrocephalus. TRIP6 carries numerous protein interaction domains and its functions require homodimerization. Indeed, TRIP6 disruption in vitro (in a choroid plexus epithelial cell line), via RNAi or inhibition of its homodimerization, confirms its function in ciliogenesis. Using super-resolution microscopy, we demonstrate TRIP6 localization at the pericentriolar material and along the ciliary axoneme. The requirement for homodimerization which doubles its interaction sites, its punctate localization along the axoneme, and its co-localization with other cilia components suggest a scaffold/co-transporter function for TRIP6 in cilia. Thus, this work uncovers an essential role of a LIM-domain protein assembly factor in mammalian ciliogenesis.
Highlights
TRIP6, a member of the ZYXIN-family of LIM domain proteins, is a focal adhesion component
Immunostaining of the protein confirmed the in situ hybridization (ISH) data and identified the exact region and cell type expressing TRIP6: a thin layer of cells bordering the ventricles in the ventricular zone (VZ)—likely ependymal cells—and epithelial cells in the choroid plexus anlage, both during embryogenesis (Supplementary Fig. 1c) and postnatally (Fig. 1b)
We report that the LIM domain protein TRIP6 promotes the differentiation of ependyma in the developing mouse brain
Summary
TRIP6, a member of the ZYXIN-family of LIM domain proteins, is a focal adhesion component. A family of scaffold proteins, carrying several protein interaction domains, serves as platform for protein–protein interactions: the sevenmember ZYXIN LIM domain family[6] including ZYXIN, lipomapreferred partner LPP, AJUBA, WNT interacting protein WTIP, LIMD1, MIGFILIN, and thyroid hormone receptor interacting protein (TRIP6) Most of these proteins localize at focal adhesions and adherens junctions, compatible with their reported role in the assembly of adhesion complexes (as first described to be localized in cell–matrix adhesions by Beckerle[7]). Their interaction partners and the cellular functions of these complexes, from actin organization/cell migration[8,9,10] through tension sensing[11,12,13] to signal transduction[14,15], have been elaborated in numerous cell culture experiments. Investigation into the underlying etiology led us to the discovery of an unexpected function of TRIP6 in brain ciliogenesis
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