title: The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium.
abstract: Mutations in RPGRIP1L result in severe human diseases called ciliopathies. To unravel the molecular function of RPGRIP1L, we analyzed Rpgrip1l(-/-) mouse embryos, which display a ciliopathy phenotype and die, at the latest, around birth. In these embryos, cilia-mediated signaling was severely disturbed. Defects in Shh signaling suggested that the Rpgrip1l deficiency causes an impairment of protein degradation and protein processing. 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. Quantifications of proteasomal substrates demonstrated that Rpgrip1l regulates proteasomal activity specifically at the basal body. Our study suggests that Rpgrip1l controls ciliary signaling by regulating the activity of the ciliary proteasome via Psmd2.
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany Christoph.Gerhardt@hhu.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gerhardt
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Johanna Maria
authors.initials: JM
authors.lastname: Lier
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Burmühl
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Struchtrup
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Deutschmann
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Vetter
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Tristan
authors.initials: T
authors.lastname: Leu
authors.affiliation: Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller University Jena, 07743 Jena, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reeg
authors.affiliation: Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller University Jena, 07743 Jena, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Rüther
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D018385:Centrosome; D002923:Cilia / Q000201:enzymology*; D005260:Female; D008297:Male; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008938:Mitosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C523257:Ftm protein, mouse; D021122:Protein Subunits; D046988:Proteasome Endopeptidase Complex