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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.

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Components of the S19 and S20 proteasomal subunits localize at primary cilia. (A–E) Immunofluorescence on MEFs of E12.5 WT and Rpgrip1l−/− embryos. Higher resolution was achieved by using SIM. The ciliary axoneme is marked by acetylated α-tubulin (blue). The TZ is marked by Tctn2 (A) or Rpgrip1l (B and C). (D and E) The ciliary axoneme is marked by acetylated α-tubulin (green) and the BB by γ-tubulin (blue). Psma5 is shown in red. (D) Z-stack of the single optical sections from E with the appropriate plot of the depicted representative image. Bars: (A–C) 0.5 µm; (D and E) 1 µm.
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fig5: Components of the S19 and S20 proteasomal subunits localize at primary cilia. (A–E) Immunofluorescence on MEFs of E12.5 WT and Rpgrip1l−/− embryos. Higher resolution was achieved by using SIM. The ciliary axoneme is marked by acetylated α-tubulin (blue). The TZ is marked by Tctn2 (A) or Rpgrip1l (B and C). (D and E) The ciliary axoneme is marked by acetylated α-tubulin (green) and the BB by γ-tubulin (blue). Psma5 is shown in red. (D) Z-stack of the single optical sections from E with the appropriate plot of the depicted representative image. Bars: (A–C) 0.5 µm; (D and E) 1 µm.

Mentions: A prerequisite for a proteasome to function at the base of cilia is the presence of components of the 19S and 20S proteasomal subunits. Psmd2, Psmd3, and Psmd4, which are components of the 19S proteasomal subunit, are found at the BB of WT MEF cilia by using 3D-SIM (Fig. 5, A–C), supporting the assumed existence of a ciliary proteasome. Psma5, which is a component of the 20S proteasomal subunit is detected at the ciliary base (BB as well as TZ) and along the axoneme of WT MEFs (Fig. 5, D and E), indicating a transport of Psma5 through the cilium. Assuming a transport of Psma5 along the cilium, we propose the BB as the location were the ciliary proteasome localizes and functions. This is the most likely scenario because we never detected components of the 19S proteasomal subunit along the axoneme of MEF 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)

Components of the S19 and S20 proteasomal subunits localize at primary cilia. (A–E) Immunofluorescence on MEFs of E12.5 WT and Rpgrip1l−/− embryos. Higher resolution was achieved by using SIM. The ciliary axoneme is marked by acetylated α-tubulin (blue). The TZ is marked by Tctn2 (A) or Rpgrip1l (B and C). (D and E) The ciliary axoneme is marked by acetylated α-tubulin (green) and the BB by γ-tubulin (blue). Psma5 is shown in red. (D) Z-stack of the single optical sections from E with the appropriate plot of the depicted representative image. Bars: (A–C) 0.5 µm; (D and E) 1 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4494006&req=5

fig5: Components of the S19 and S20 proteasomal subunits localize at primary cilia. (A–E) Immunofluorescence on MEFs of E12.5 WT and Rpgrip1l−/− embryos. Higher resolution was achieved by using SIM. The ciliary axoneme is marked by acetylated α-tubulin (blue). The TZ is marked by Tctn2 (A) or Rpgrip1l (B and C). (D and E) The ciliary axoneme is marked by acetylated α-tubulin (green) and the BB by γ-tubulin (blue). Psma5 is shown in red. (D) Z-stack of the single optical sections from E with the appropriate plot of the depicted representative image. Bars: (A–C) 0.5 µm; (D and E) 1 µm.
Mentions: A prerequisite for a proteasome to function at the base of cilia is the presence of components of the 19S and 20S proteasomal subunits. Psmd2, Psmd3, and Psmd4, which are components of the 19S proteasomal subunit, are found at the BB of WT MEF cilia by using 3D-SIM (Fig. 5, A–C), supporting the assumed existence of a ciliary proteasome. Psma5, which is a component of the 20S proteasomal subunit is detected at the ciliary base (BB as well as TZ) and along the axoneme of WT MEFs (Fig. 5, D and E), indicating a transport of Psma5 through the cilium. Assuming a transport of Psma5 along the cilium, we propose the BB as the location were the ciliary proteasome localizes and functions. This is the most likely scenario because we never detected components of the 19S proteasomal subunit along the axoneme of MEF 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