The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium.
Bottom Line: Mutations in RPGRIP1L result in severe human diseases called ciliopathies.Indeed, we detected a cilia-dependent decreased proteasomal activity in the absence of Rpgrip1l.We found different proteasomal components localized to cilia and identified Psmd2, a component of the regulatory proteasomal 19S subunit, as an interaction partner for Rpgrip1l.
Affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany Christoph.Gerhardt@hhu.de.Show MeSH
Related in: MedlinePlus
License 1 - License 2
Mentions: The absence of particular TZ proteins results in differences in ciliary length (Tammachote et al., 2009; Cui et al., 2011; Dowdle et al., 2011; Garcia-Gonzalo et al., 2011). Such alterations are indicative for ciliary signaling defects (Cui et al., 2011; Dowdle et al., 2011; Garcia-Gonzalo et al., 2011; Ishikawa and Marshall, 2011; Larkins et al., 2011). We measured the length of cilia in Rpgrip1l−/− MEFs and in different organs of Rpgrip1l−/− mouse embryos by using immunofluorescence. Although the cilia in Rpgrip1l−/− MEFs, limbs, livers, and lungs are significantly longer, the length of cardiac cilia is significantly reduced (Fig. 2 A). We evaluated the quality of our fluorescence-based ciliary length measurements by comparing these results with previously published scanning EM (SEM) data. The absolute value we measured for wild-type (WT) limb cilia is 1.25 ± 0.05 µm (standard error of the mean; Fig. 2 C), which correlates with SEM quantifications (Haycraft et al., 2005; Moon et al., 2014). Moreover, we performed SEM analyses to quantify the length of Rpgrip1l−/− limb cilia. The elongation of limb cilia, in the absence of Rpgrip1l, was verified by these SEM experiments (Fig. 2, B and C).
Affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany Christoph.Gerhardt@hhu.de.