Fbxo41 Promotes Disassembly of Neuronal Primary Cilia

Cillian R. King, Ana R. A. A. Quadros, Anaël Chazeau, Ingrid Saarloos, Anne Jolien van der Graaf, Matthijs Verhage, Ruud F. Toonen*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Neuronal primary cilia are signaling organelles with crucial roles in brain development and disease. Cilia structure is decisive for their signaling capacities but the mechanisms regulating it are poorly understood. We identify Fbxo41 as a novel Skp1/Cullin1/F-box (SCF) E3-ligase complex subunit that targets to neuronal centrioles where its accumulation promotes disassembly of primary cilia, and affects sonic hedgehog signaling, a canonical ciliary pathway. Fbxo41 targeting to centrioles requires its Coiled-coil and F-box domains. Levels of Fbxo41 at the centrioles inversely correlate with neuronal cilia length, and mutations that disrupt Fbxo41 targeting or assembly into SCF-complexes also disturb its function in cilia disassembly and signaling. Fbxo41 dependent cilia disassembly in mitotic and post-mitotic cells requires rearrangements of the actin-cytoskeleton, but requires Aurora A kinase activation only in mitotic cells, highlighting important mechanistical differences controlling cilia size between mitotic and post-mitotic cells. Phorbol esters induce recruitment of overexpressed Fbxo41 to centrioles and cilia disassembly in neurons, but disassembly can also occur in absence of Fbxo41. We propose that Fbxo41 targeting to centrosomes regulates neuronal cilia structure and signaling capacity in addition to Fbxo41-independent pathways controlling cilia size.

Original languageEnglish
Article number8179
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2019


We are grateful to Robbert Zalm, Joost Hoetjes and Frank Den Oudsten for production of lentiviral particles, Desiree Schut for culturing of primary neurons, Jurjen Broeke for technical assistance and other members of the Toonen laboratory for helpful discussions. This work was supported by the Netherlands Organization for Scientific Research (ZonMw-VENI 916-66-101, ZonMW-TOP 91208017 to RFT; Pionier/VICI 900-01-001 and ZonMW 903-42-095 to MV) and by the EU (EUROSPIN project HEALTH-F2-2009-241498 to CRK and MV, and CognitionNet FP7-ITN-607508 to ARAAQ).

FundersFunder number
Netherlands Organization for Scientific ResearchZonMW 903-42-095, ZonMW-TOP 91208017, ZonMw-VENI 916-66-101, Pionier/VICI 900-01-001
Seventh Framework Programme241498, 607508
European CommissionHEALTH-F2-2009-241498
ZonMwTOP 91208017, VENI 916-66-101


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