MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis

Corey L. Williams, Chunmei Li, Katarzyna Kida, Peter N. Inglis, Swetha Mohan, Lucie Semenec, Nathan J. Bialas, Rachel M. Stupay, Nansheng Chen, Oliver E. Blacque, Bradley K. Yoder, Michel R. Leroux*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

296 Citations (Scopus)
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Abstract

Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and related ciliopathies present with overlapping phenotypes and display considerable allelism between at least twelve different genes of largely unexplained function. We demonstrate that the conserved C. elegans B9 domain (MKS-1, MKSR-1, and MKSR-2), MKS-3/TMEM67, MKS-5/RPGRIP1L, MKS-6/CC2D2A, NPHP-1, and NPHP-4 proteins exhibit essential, collective functions at the transition zone (TZ), an under-appreciated region at the base of all cilia characterized by Y-shaped assemblages that link axoneme microtubules to surrounding membrane. These TZ proteins functionally interact as members of two distinct modules, which together contribute to an early ciliogenic event. Specifically, MKS/MKSR/NPHP proteins establish basal body/TZ membrane attachments before or coinciding with intraflagellar transport-dependent axoneme extension and subsequently restrict accumulation of nonciliary components within the ciliary compartment. Together, our findings uncover a unified role for eight TZ-localized proteins in basal body anchoring and establishing a ciliary gate during ciliogenesis, and suggest that disrupting ciliary gate function contributes to phenotypic features of the MKS/NPHP disease spectrum.

Original languageEnglish
Pages (from-to)1023-1041
Number of pages19
JournalJournal of Cell Biology
Volume192
Issue number6
DOIs
Publication statusPublished - 21 Mar 2011
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2011. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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