Novel function of TRIP6, in brain ciliogenesis

Abstract

TRIP6, a member of the zyxin-family of LIM domain proteins, is a focal adhesion component. trip6 deletion in the mouse revealed, unexpectedly, in view of its ubiquitous expression, a function in the brain: ependymal and choroid plexus epithelial cells were poorly developed, carrying fewer and shorter cilia, and the mice developed hydrocephalus. TRIP6 disruption, via RNAi or inhibition of its homodimerization, in a choroid plexus epithelial cell line, confirmed its function in ciliogenesis. Zyxin-family members carry numerous protein interaction domains. In common with assembly of other multiprotein complexes, ciliogenesis may be facilitated by molecular assembly factors. Super-resolution microscopy demonstrated 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. This is the first discovery of a protein assembly factor essential for mammalian ciliogenesis.

The LIM domain protein nTRIP6 modulates the dynamics of myogenic differentiation

“…The main function of the cytosolic isoform TRIP6 is to regulate adhesion and migration 21 , 23 , a property shared by other members of the ZYXIN family of focal adhesion LIM domain proteins 40 . However, no general phenotype was observed upon the total deletion of the Trip6 gene in the mouse, as could have been expected from the loss of such an important function 34 . This observation, together with the absence of overt phenotypes in mice with deletion of the genes for ZYXIN 41 , LPP 42 , Ajuba 43 , LIMD1 44 , and Migfilin 45 , strongly suggests a redundancy in the function of TRIP6 and other family members in the cytosol.…”

“…To investigate the relevance of these findings for muscle regeneration in vivo, we generated a mouse line, C57BL/6J- Trip6 Tm(loxP) hereafter referred to as Trip6 fl/fl , in which the Trip6 gene is conditionally targeted by flanking exons 2 to 9 by loxP sites 34 . These mice were crossed with C57BL/6J- Pax7 tm1(Cre-ERT2)Gaka mice (short name Pax7 Cre-ERT2 ), in which the tamoxifen-inducible version of Cre-recombinase (Cre-ERT2) was knocked into the Pax7 locus 35 .…”

“…C57BL/6 J- Pax7 tm1(Cre-ERT2)Gaka mice, hereafter referred to as Pax7 Cre-ERT2 , in which the tamoxifen-inducible version of Cre-recombinase (Cre-ERT2) was knocked in the Pax7 locus 35 were kindly provided by Gabrielle Kardon (University of Utah, Salt Lake City, UT) and Daniel Metzger (IGBMC, Strasbourg, France). The generation of the Trip6 floxed mouse line (C57BL/6 J- Trip6 Tm(loxP) hereafter referred to as Trip6 fl/fl ) has been described 34 . Trip6 fl/fl were crossed to Pax7 Cre-ERT2 and Trip6 fl/fl and Trip6 fl/fl ; Pax7 Cre-ERT2/wt offspring were identified by PCR genotyping on tail DNA.…”

Cytoskeletal protein Zyxin in embryonic development: from controlling cell movements and pluripotency to regulating embryonic patterning

“…Interestingly, Zyxin, as well as its homologs, Trip6 and Lpp were found recently in the content of key membrane‐associated proteins in primary cilia [40,41]. At the same time, it was established that the activity of Shh signalling, including the functioning its Gli‐family effectors, is also tightly associated with the formation of primary cilia [42,43].…”