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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
03 11 2022
Historique:
received: 06 08 2021
accepted: 03 10 2022
entrez: 4 11 2022
pubmed: 5 11 2022
medline: 8 11 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36329026
doi: 10.1038/s41467-022-33820-w
pii: 10.1038/s41467-022-33820-w
pmc: PMC9633640
doi:

Substances chimiques

Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6595

Subventions

Organisme : CIHR
ID : PJT-156042
Pays : Canada

Investigateurs

J C Ambrose (JC)
P Arumugam (P)
R Bevers (R)
M Bleda (M)
F Boardman-Pretty (F)
C R Boustred (CR)
H Brittain (H)
M A Brown (MA)
M J Caulfield (MJ)
G C Chan (GC)
A Giess (A)
J N Griffin (JN)
A Hamblin (A)
S Henderson (S)
T J P Hubbard (TJP)
R Jackson (R)
L J Jones (LJ)
D Kasperaviciute (D)
M Kayikci (M)
A Kousathanas (A)
L Lahnstein (L)
A Lakey (A)
S E A Leigh (SEA)
I U S Leong (IUS)
F J Lopez (FJ)
F Maleady-Crowe (F)
M McEntagart (M)
F Minneci (F)
J Mitchell (J)
L Moutsianas (L)
M Mueller (M)
N Murugaesu (N)
A C Need (AC)
P O'Donovan (P)
C A Odhams (CA)
C Patch (C)
D Perez-Gil (D)
M B Pereira (MB)
J Pullinger (J)
T Rahim (T)
A Rendon (A)
T Rogers (T)
K Savage (K)
K Sawant (K)
R H Scott (RH)
A Siddiq (A)
A Sieghart (A)
S C Smith (SC)
A Sosinsky (A)
A Stuckey (A)
M Tanguy (M)
A L Taylor Tavares (AL)
E R A Thomas (ERA)
S R Thompson (SR)
A Tucci (A)
M J Welland (MJ)
E Williams (E)
K Witkowska (K)
S M Wood (SM)
M Zarowiecki (M)

Informations de copyright

© 2022. The Author(s).

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Auteurs

Paul W Chrystal (PW)

Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada. pchrysta@ualberta.ca.
Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada. pchrysta@ualberta.ca.

Nils J Lambacher (NJ)

Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, BC, Canada.

Lance P Doucette (LP)

Department of Ophthalmology & Visual Science, University of Alberta, Edmonton, AB, Canada.

James Bellingham (J)

UCL Institute of Ophthalmology, London, UK.

Elena R Schiff (ER)

Moorfields Eye Hospital, London, UK.
School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

Nicole C L Noel (NCL)

Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.

Chunmei Li (C)

Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, BC, Canada.

Sofia Tsiropoulou (S)

School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

Geoffrey A Casey (GA)

Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.

Yi Zhai (Y)

Department of Ophthalmology & Visual Science, University of Alberta, Edmonton, AB, Canada.

Nathan J Nadolski (NJ)

Division of Anatomy, Department of Surgery, University of Alberta, Edmonton, AB, Canada.

Mohammed H Majumder (MH)

Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.

Julia Tagoe (J)

Lethbridge Outreach Genetics Service, Alberta Health Services, Lethbridge, AB, Canada.

Fabiana D'Esposito (F)

Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK.
ICORG, Imperial College London, London, UK.

Maria Francesca Cordeiro (MF)

ICORG, Imperial College London, London, UK.

Susan Downes (S)

Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Jill Clayton-Smith (J)

Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK.

Jamie Ellingford (J)

Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, UK.
Genomics England, London, UK.

Omar A Mahroo (OA)

UCL Institute of Ophthalmology, London, UK.
Moorfields Eye Hospital, London, UK.

Jennifer C Hocking (JC)

Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
Division of Anatomy, Department of Surgery, University of Alberta, Edmonton, AB, Canada.
Department of Cell Biology, University of Alberta, Edmonton, AB, Canada.
Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada.

Michael E Cheetham (ME)

UCL Institute of Ophthalmology, London, UK.

Andrew R Webster (AR)

UCL Institute of Ophthalmology, London, UK.
Moorfields Eye Hospital, London, UK.

Gert Jansen (G)

Department of Cell Biology, Erasmus University Medical Centre, Rotterdam, The Netherlands.

Oliver E Blacque (OE)

School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

W Ted Allison (WT)

Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada. ted.allison@ualberta.ca.
Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada. ted.allison@ualberta.ca.

Ping Yee Billie Au (PYB)

Department of Medical Genetics, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. ping-yee.au@albertahealthservices.ca.

Ian M MacDonald (IM)

Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada. macdonal@ualberta.ca.
Department of Ophthalmology & Visual Science, University of Alberta, Edmonton, AB, Canada. macdonal@ualberta.ca.

Gavin Arno (G)

UCL Institute of Ophthalmology, London, UK. g.arno@ucl.ac.uk.
Moorfields Eye Hospital, London, UK. g.arno@ucl.ac.uk.
North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. g.arno@ucl.ac.uk.

Michel R Leroux (MR)

Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada. leroux@sfu.ca.
Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, BC, Canada. leroux@sfu.ca.

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