The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.

TitleThe ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.
Publication TypeJournal Article
Year of Publication2016
AuthorsToriyama, M, Lee, C, S Taylor, P, Duran, I, Cohn, DH, Bruel, A-L, Tabler, JM, Drew, K, Kelly, MR, Kim, S, Park, TJoo, Braun, DA, Pierquin, G, Biver, A, Wagner, K, Malfroot, A, Panigrahi, I, Franco, B, Al-Lami, HAdel, Yeung, Y, Choi, YJa, Duffourd, Y, Faivre, L, Rivière, J-B, Chen, J, Liu, KJ, Marcotte, EM, Hildebrandt, F, Thauvin-Robinet, C, Krakow, D, Jackson, PK, Wallingford, JB
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics
JournalNat Genet
Volume48
Issue6
Pagination648-56
Date Published2016 Jun
ISSN1546-1718
Abstract

Cilia use microtubule-based intraflagellar transport (IFT) to organize intercellular signaling. Ciliopathies are a spectrum of human diseases resulting from defects in cilia structure or function. The mechanisms regulating the assembly of ciliary multiprotein complexes and the transport of these complexes to the base of cilia remain largely unknown. Combining proteomics, in vivo imaging and genetic analysis of proteins linked to planar cell polarity (Inturned, Fuzzy and Wdpcp), we identified and characterized a new genetic module, which we term CPLANE (ciliogenesis and planar polarity effector), and an extensive associated protein network. CPLANE proteins physically and functionally interact with the poorly understood ciliopathy-associated protein Jbts17 at basal bodies, where they act to recruit a specific subset of IFT-A proteins. In the absence of CPLANE, defective IFT-A particles enter the axoneme and IFT-B trafficking is severely perturbed. Accordingly, mutation of CPLANE genes elicits specific ciliopathy phenotypes in mouse models and is associated with ciliopathies in human patients.

DOI10.1038/ng.3558
Alternate JournalNat. Genet.
PubMed ID27158779
PubMed Central IDPMC4978421
Grant ListMR/L017237/1 / / Medical Research Council / United Kingdom
RC2 HL102923 / HL / NHLBI NIH HHS / United States
U54 HG006493 / HG / NHGRI NIH HHS / United States
UC2 HL102926 / HL / NHLBI NIH HHS / United States
UC2 HL103010 / HL / NHLBI NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
RC2 HL102926 / HL / NHLBI NIH HHS / United States
DP1 GM106408 / GM / NIGMS NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
R01 GM086627 / GM / NIGMS NIH HHS / United States
RC2 HL102924 / HL / NHLBI NIH HHS / United States
R01 AR061485 / AR / NIAMS NIH HHS / United States
R01 HL117164 / HL / NHLBI NIH HHS / United States
R01 DK068306 / DK / NIDDK NIH HHS / United States
R01 GM114276 / GM / NIGMS NIH HHS / United States
UC2 HL102923 / HL / NHLBI NIH HHS / United States
UC2 HL102924 / HL / NHLBI NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
RC2 HL103010 / HL / NHLBI NIH HHS / United States
R01 AR066124 / AR / NIAMS NIH HHS / United States
R01 AR062651 / AR / NIAMS NIH HHS / United States
RC2 HL102925 / HL / NHLBI NIH HHS / United States
UC2 HL102925 / HL / NHLBI NIH HHS / United States
F32 GM112495 / GM / NIGMS NIH HHS / United States