?

Subcellular localization

basal body, Nucleoplasm, Cytokinetic bridge, Centriolar satellite, Cytosol, Flagellar centriole

Functional category

• Protein processing & maturation
• Non-motile cilium / primary cilium
• Trafficking (BBSome
• small GTPases
• vesicular transport
• ATPases)

Function

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. 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. 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.(26150391).