Limits...
The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium.

Gerhardt C, Lier JM, Burmühl S, Struchtrup A, Deutschmann K, Vetter M, Leu T, Reeg S, Grune T, Rüther U - J. Cell Biol. (2015)

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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany Christoph.Gerhardt@hhu.de.

Show MeSH

Related in: MedlinePlus

Rpgrip1l deficiency results in an accumulation of proteasomal subunit components at the base of cilia. (A–D) Immunofluorescence on MEFs of E12.5 WT and Rpgrip1l−/− embryos (both genotypes: Psmd2, n = 7 embryos; Psmd3, n = 3 embryos; Psmd4, n = 3 embryos; Psma5, n = 5 embryos). At least 10 cilia per embryo were used for Psmd2, Psmd3, and Psmd4 quantification, respectively, and 20 cilia per embryo were used for Psma5 quantification. The ciliary axoneme is marked by acetylated α-tubulin (green). The BB is marked by Pcnt (green; white arrowheads; A) or γ-tubulin (blue; B–D). Error bars show standard error of the mean. *, P < 0.05; ***, P < 0.001. Bars: (A, B, and D) 1 µm; (C) 0.5 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4494006&req=5

fig6: Rpgrip1l deficiency results in an accumulation of proteasomal subunit components at the base of cilia. (A–D) Immunofluorescence on MEFs of E12.5 WT and Rpgrip1l−/− embryos (both genotypes: Psmd2, n = 7 embryos; Psmd3, n = 3 embryos; Psmd4, n = 3 embryos; Psma5, n = 5 embryos). At least 10 cilia per embryo were used for Psmd2, Psmd3, and Psmd4 quantification, respectively, and 20 cilia per embryo were used for Psma5 quantification. The ciliary axoneme is marked by acetylated α-tubulin (green). The BB is marked by Pcnt (green; white arrowheads; A) or γ-tubulin (blue; B–D). Error bars show standard error of the mean. *, P < 0.05; ***, P < 0.001. Bars: (A, B, and D) 1 µm; (C) 0.5 µm.

Mentions: It has been reported that inhibition of the proteasome leads to an accumulation of proteasomal subunits at the centrosome (Fabunmi et al., 2000). So the question arises whether proteasomal components accumulate in a significantly higher amount at the ciliary base of Rpgrip1l−/− MEFs. All analyzed proteasomal components, Psmd2, Psmd3, Psmd4 and Psma5, were significantly increased at the ciliary base in Rpgrip1l−/− MEFs (Fig. 6, A–D), underscoring the likelihood that Rpgrip1l deficiency affects proteasomal activity at primary cilia.


The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium.

Gerhardt C, Lier JM, Burmühl S, Struchtrup A, Deutschmann K, Vetter M, Leu T, Reeg S, Grune T, Rüther U - J. Cell Biol. (2015)

Rpgrip1l deficiency results in an accumulation of proteasomal subunit components at the base of cilia. (A–D) Immunofluorescence on MEFs of E12.5 WT and Rpgrip1l−/− embryos (both genotypes: Psmd2, n = 7 embryos; Psmd3, n = 3 embryos; Psmd4, n = 3 embryos; Psma5, n = 5 embryos). At least 10 cilia per embryo were used for Psmd2, Psmd3, and Psmd4 quantification, respectively, and 20 cilia per embryo were used for Psma5 quantification. The ciliary axoneme is marked by acetylated α-tubulin (green). The BB is marked by Pcnt (green; white arrowheads; A) or γ-tubulin (blue; B–D). Error bars show standard error of the mean. *, P < 0.05; ***, P < 0.001. Bars: (A, B, and D) 1 µm; (C) 0.5 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4494006&req=5

fig6: Rpgrip1l deficiency results in an accumulation of proteasomal subunit components at the base of cilia. (A–D) Immunofluorescence on MEFs of E12.5 WT and Rpgrip1l−/− embryos (both genotypes: Psmd2, n = 7 embryos; Psmd3, n = 3 embryos; Psmd4, n = 3 embryos; Psma5, n = 5 embryos). At least 10 cilia per embryo were used for Psmd2, Psmd3, and Psmd4 quantification, respectively, and 20 cilia per embryo were used for Psma5 quantification. The ciliary axoneme is marked by acetylated α-tubulin (green). The BB is marked by Pcnt (green; white arrowheads; A) or γ-tubulin (blue; B–D). Error bars show standard error of the mean. *, P < 0.05; ***, P < 0.001. Bars: (A, B, and D) 1 µm; (C) 0.5 µm.
Mentions: It has been reported that inhibition of the proteasome leads to an accumulation of proteasomal subunits at the centrosome (Fabunmi et al., 2000). So the question arises whether proteasomal components accumulate in a significantly higher amount at the ciliary base of Rpgrip1l−/− MEFs. All analyzed proteasomal components, Psmd2, Psmd3, Psmd4 and Psma5, were significantly increased at the ciliary base in Rpgrip1l−/− MEFs (Fig. 6, A–D), underscoring the likelihood that Rpgrip1l deficiency affects proteasomal activity at primary cilia.

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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany Christoph.Gerhardt@hhu.de.

Show MeSH
Related in: MedlinePlus