The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision

Paul W. Chrystal; Nils J. Lambacher; Genomics England Research Consortium; Lance P. Doucette; James Bellingham; Elena R. Schiff; Nicole C.L. Noel; Chunmei Li; Sofia Tsiropoulou; Geoffrey A. Casey; Yi Zhai; Nathan J. Nadolski; Mohammed H. Majumder; Julia Tagoe; Fabiana D’Esposito; Maria Francesca Cordeiro; Susan Downes; Jill Clayton-Smith; Jamie Ellingford; J. C. Ambrose; P. Arumugam; R. Bevers; M. Bleda; F. Boardman-Pretty; C. R. Boustred; H. Brittain; M. A. Brown; M. J. Caulfield; G. C. Chan; A. Giess; J. N. Griffin; A. Hamblin; S. Henderson; T. J.P. Hubbard; R. Jackson; L. J. Jones; D. Kasperaviciute; M. Kayikci; A. Kousathanas; L. Lahnstein; A. Lakey; S. E.A. Leigh; I. U.S. Leong; F. J. Lopez; J. Mitchell; M. B. Pereira; S. C. Smith; E. R.A. Thomas; S. R. Thompson; Gert Jansen; Gavin Arno; M. R. Leroux

doi:10.1038/s41467-022-33820-w

The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision

Paul W. Chrystal^*, Nils J. Lambacher, Genomics England Research Consortium, Lance P. Doucette, James Bellingham, Elena R. Schiff, Nicole C.L. Noel, Chunmei Li, Sofia Tsiropoulou, Geoffrey A. Casey, Yi Zhai, Nathan J. Nadolski, Mohammed H. Majumder, Julia Tagoe, Fabiana D’Esposito, Maria Francesca Cordeiro, Susan Downes, Jill Clayton-Smith, Jamie Ellingford, J. C. AmbroseP. Arumugam, R. Bevers, M. Bleda, F. Boardman-Pretty, C. R. Boustred, H. Brittain, M. A. Brown, M. J. Caulfield, G. C. Chan, A. Giess, J. N. Griffin, A. Hamblin, S. Henderson, T. J.P. Hubbard, R. Jackson, L. J. Jones, D. Kasperaviciute, M. Kayikci, A. Kousathanas, L. Lahnstein, A. Lakey, S. E.A. Leigh, I. U.S. Leong, F. J. Lopez, J. Mitchell, M. B. Pereira, S. C. Smith, E. R.A. Thomas, S. R. Thompson, Gert Jansen, Gavin Arno, M. R. Leroux

^*Corresponding author for this work

Cell biology

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Abstract

Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes. We demonstrate that in zebrafish, cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy. Hence, CFAP20 functions within a structural/functional hub centered on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associated domains or macromolecular complexes. Our findings suggest an uncharacterised pathomechanism for retinal dystrophy, and potentially for motile and non-motile ciliopathies in general.

Original language	English
Article number	6595
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-33820-w
Publication status	Published - 3 Nov 2022

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Publisher Copyright:
© 2022, The Author(s).

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The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for visionFinal published version, 8.78 MBLicence: CC BY

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Chrystal, P. W., Lambacher, N. J., Genomics England Research Consortium, Doucette, L. P., Bellingham, J., Schiff, E. R., Noel, N. C. L., Li, C., Tsiropoulou, S., Casey, G. A., Zhai, Y., Nadolski, N. J., Majumder, M. H., Tagoe, J., D’Esposito, F., Cordeiro, M. F., Downes, S., Clayton-Smith, J., Ellingford, J., ... Leroux, M. R. (2022). The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision. Nature Communications, 13(1), Article 6595. https://doi.org/10.1038/s41467-022-33820-w

@article{7d88acafb7cd4795bd09ef3b43de8b58,

title = "The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision",

abstract = "Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes. We demonstrate that in zebrafish, cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy. Hence, CFAP20 functions within a structural/functional hub centered on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associated domains or macromolecular complexes. Our findings suggest an uncharacterised pathomechanism for retinal dystrophy, and potentially for motile and non-motile ciliopathies in general.",

author = "Chrystal, {Paul W.} and Lambacher, {Nils J.} and {Genomics England Research Consortium} and Doucette, {Lance P.} and James Bellingham and Schiff, {Elena R.} and Noel, {Nicole C.L.} and Chunmei Li and Sofia Tsiropoulou and Casey, {Geoffrey A.} and Yi Zhai and Nadolski, {Nathan J.} and Majumder, {Mohammed H.} and Julia Tagoe and Fabiana D{\textquoteright}Esposito and Cordeiro, {Maria Francesca} and Susan Downes and Jill Clayton-Smith and Jamie Ellingford and Ambrose, {J. C.} and P. Arumugam and R. Bevers and M. Bleda and F. Boardman-Pretty and Boustred, {C. R.} and H. Brittain and Brown, {M. A.} and Caulfield, {M. J.} and Chan, {G. C.} and A. Giess and Griffin, {J. N.} and A. Hamblin and S. Henderson and Hubbard, {T. J.P.} and R. Jackson and Jones, {L. J.} and D. Kasperaviciute and M. Kayikci and A. Kousathanas and L. Lahnstein and A. Lakey and Leigh, {S. E.A.} and Leong, {I. U.S.} and Lopez, {F. J.} and J. Mitchell and Pereira, {M. B.} and Smith, {S. C.} and Thomas, {E. R.A.} and Thompson, {S. R.} and Gert Jansen and Gavin Arno and Leroux, {M. R.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = nov,

day = "3",

doi = "10.1038/s41467-022-33820-w",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Chrystal, PW, Lambacher, NJ, Genomics England Research Consortium, Doucette, LP, Bellingham, J, Schiff, ER, Noel, NCL, Li, C, Tsiropoulou, S, Casey, GA, Zhai, Y, Nadolski, NJ, Majumder, MH, Tagoe, J, D’Esposito, F, Cordeiro, MF, Downes, S, Clayton-Smith, J, Ellingford, J, Ambrose, JC, Arumugam, P, Bevers, R, Bleda, M, Boardman-Pretty, F, Boustred, CR, Brittain, H, Brown, MA, Caulfield, MJ, Chan, GC, Giess, A, Griffin, JN, Hamblin, A, Henderson, S, Hubbard, TJP, Jackson, R, Jones, LJ, Kasperaviciute, D, Kayikci, M, Kousathanas, A, Lahnstein, L, Lakey, A, Leigh, SEA, Leong, IUS, Lopez, FJ, Mitchell, J, Pereira, MB, Smith, SC, Thomas, ERA, Thompson, SR, Jansen, G, Arno, G & Leroux, MR 2022, 'The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision', Nature Communications, vol. 13, no. 1, 6595. https://doi.org/10.1038/s41467-022-33820-w

TY - JOUR

T1 - The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision

AU - Chrystal, Paul W.

AU - Lambacher, Nils J.

AU - Genomics England Research Consortium

AU - Doucette, Lance P.

AU - Bellingham, James

AU - Schiff, Elena R.

AU - Noel, Nicole C.L.

AU - Li, Chunmei

AU - Tsiropoulou, Sofia

AU - Casey, Geoffrey A.

AU - Zhai, Yi

AU - Nadolski, Nathan J.

AU - Majumder, Mohammed H.

AU - Tagoe, Julia

AU - D’Esposito, Fabiana

AU - Cordeiro, Maria Francesca

AU - Downes, Susan

AU - Clayton-Smith, Jill

AU - Ellingford, Jamie

AU - Ambrose, J. C.

AU - Arumugam, P.

AU - Bevers, R.

AU - Bleda, M.

AU - Boardman-Pretty, F.

AU - Boustred, C. R.

AU - Brittain, H.

AU - Brown, M. A.

AU - Caulfield, M. J.

AU - Chan, G. C.

AU - Giess, A.

AU - Griffin, J. N.

AU - Hamblin, A.

AU - Henderson, S.

AU - Hubbard, T. J.P.

AU - Jackson, R.

AU - Jones, L. J.

AU - Kasperaviciute, D.

AU - Kayikci, M.

AU - Kousathanas, A.

AU - Lahnstein, L.

AU - Lakey, A.

AU - Leigh, S. E.A.

AU - Leong, I. U.S.

AU - Lopez, F. J.

AU - Mitchell, J.

AU - Pereira, M. B.

AU - Smith, S. C.

AU - Thomas, E. R.A.

AU - Thompson, S. R.

AU - Jansen, Gert

AU - Arno, Gavin

AU - Leroux, M. R.

PY - 2022/11/3

Y1 - 2022/11/3

N2 - Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes. We demonstrate that in zebrafish, cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy. Hence, CFAP20 functions within a structural/functional hub centered on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associated domains or macromolecular complexes. Our findings suggest an uncharacterised pathomechanism for retinal dystrophy, and potentially for motile and non-motile ciliopathies in general.

AB - Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes. We demonstrate that in zebrafish, cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy. Hence, CFAP20 functions within a structural/functional hub centered on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associated domains or macromolecular complexes. Our findings suggest an uncharacterised pathomechanism for retinal dystrophy, and potentially for motile and non-motile ciliopathies in general.

UR - http://www.scopus.com/inward/record.url?scp=85141179000&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-33820-w

DO - 10.1038/s41467-022-33820-w

M3 - Article

C2 - 36329026

AN - SCOPUS:85141179000

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 6595

ER -

The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision

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