KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Anna AWM Sanders
  • Erik de Vrieze
  • Anas M Alazami
  • Fatema Alzahrani
  • Erik B Malarkey
  • Nasrin Sorusch
  • Lars Tebbe
  • Stefanie Kuhns
  • Teunis JP van Dam
  • Amal Alhashem
  • Brahim Tabarki
  • Qianhao Lu
  • Nils J Lambacher
  • Julie E Kennedy
  • Rachel V Bowie
  • Lisette Hetterschijt
  • Sylvia van Beersum
  • Jeroen van Reeuwijk
  • Karsten Boldt
  • Hannie Kremer
  • Robert A Kesterson
  • Dorota Monies
  • Mohamed Abouelhoda
  • Ronald Roepman
  • Martijn H Huynen
  • Marius Ueffing
  • Rob B Russell
  • Uwe Wolfrum
  • Bradley K Yoder
  • Erwin van Wijk
  • Fowzan S Alkuraya
  • Oliver E Blacque
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000367324800001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1186/s13059-015-0858-z
Externe Identifier
  • Clarivate Analytics Document Solution ID: CZ8BK
  • PubMed Identifier: 26714646
ISSN
1474-760X
Zeitschrift
GENOME BIOLOGY
Schlüsselwörter
  • Joubert syndrome
  • Cilia
  • KIAA0556
  • K04F10.2
  • Microtubule
  • Katanin
  • Basal body
Artikelnummer
ARTN 293
Datum der Veröffentlichung
2015
Status
Published
Titel
KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome
Sub types
  • Article
Ausgabe der Zeitschrift
16

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Anna AWM Sanders
  • Erik de Vrieze
  • Anas M Alazami
  • Fatema Alzahrani
  • Erik B Malarkey
  • Nasrin Sorusch
  • Lars Tebbe
  • Stefanie Kuhns
  • Teunis JP van Dam
  • Amal Alhashem
  • Brahim Tabarki
  • Qianhao Lu
  • Nils J Lambacher
  • Julie E Kennedy
  • Rachel V Bowie
  • Lisette Hetterschijt
  • Sylvia van Beersum
  • Jeroen van Reeuwijk
  • Karsten Boldt
  • Hannie Kremer
  • Robert A Kesterson
  • Dorota Monies
  • Mohamed Abouelhoda
  • Ronald Roepman
  • Martijn H Huynen
  • Marius Ueffing
  • Rob B Russell
  • Uwe Wolfrum
  • Bradley K Yoder
  • Erwin van Wijk
  • Fowzan S Alkuraya
  • Oliver E Blacque
DOI
10.1186/s13059-015-0858-z
eISSN
1474-760X
Ausgabe der Veröffentlichung
1
Zeitschrift
Genome Biology
Sprache
en
Artikelnummer
293
Online publication date
2015
Datum der Veröffentlichung
2015
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1186/s13059-015-0858-z
Datum der Datenerfassung
2022
Titel
KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome
Ausgabe der Zeitschrift
16

Datenquelle: Crossref

Abstract
<h4>Background</h4>Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures.<h4>Results</h4>Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome. Patient-derived fibroblasts displayed reduced ciliogenesis potential and abnormally elongated cilia. Investigation of disease pathophysiology revealed that Kiaa0556 (-/-) null mice possess a Joubert syndrome-associated brain-restricted phenotype. Functional studies in Caenorhabditis elegans nematodes and cultured human cells support a conserved ciliary role for KIAA0556 linked to microtubule regulation. First, nematode KIAA0556 is expressed almost exclusively in ciliated cells, and the worm and human KIAA0556 proteins are enriched at the ciliary base. Second, C. elegans KIAA0056 regulates ciliary A-tubule number and genetically interacts with an ARL13B (JBTS8) orthologue to control cilium integrity. Third, human KIAA0556 binds to microtubules in vitro and appears to stabilise microtubule networks when overexpressed. Finally, human KIAA0556 biochemically interacts with ciliary proteins and p60/p80 katanins. The latter form a microtubule-severing enzyme complex that regulates microtubule dynamics as well as ciliary functions.<h4>Conclusions</h4>We have identified KIAA0556 as a novel microtubule-associated ciliary base protein mutated in Joubert syndrome. Consistent with the mild patient phenotype, our nematode, mice and human cell data support the notion that KIAA0556 has a relatively subtle and variable cilia-related function, which we propose is related to microtubule regulation.
Addresses
  • School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.
Autoren
  • Anna AWM Sanders
  • Erik de Vrieze
  • Anas M Alazami
  • Fatema Alzahrani
  • Erik B Malarkey
  • Nasrin Sorusch
  • Lars Tebbe
  • Stefanie Kuhns
  • Teunis JP van Dam
  • Amal Alhashem
  • Brahim Tabarki
  • Qianhao Lu
  • Nils J Lambacher
  • Julie E Kennedy
  • Rachel V Bowie
  • Lisette Hetterschijt
  • Sylvia van Beersum
  • Jeroen van Reeuwijk
  • Karsten Boldt
  • Hannie Kremer
  • Robert A Kesterson
  • Dorota Monies
  • Mohamed Abouelhoda
  • Ronald Roepman
  • Martijn H Huynen
  • Marius Ueffing
  • Rob B Russell
  • Rob B Russell
  • Uwe Wolfrum
  • Bradley K Yoder
  • Erwin van Wijk
  • Fowzan S Alkuraya
  • Oliver E Blacque
DOI
10.1186/s13059-015-0858-z
eISSN
1474-760X
Externe Identifier
  • PubMed Identifier: 26714646
  • PubMed Central ID: PMC4699358
Funding acknowledgements
  • Dutch Research Council (NWO): 016.136.091
  • NIDDK NIH HHS: 2P30DK074038
  • Seventh Framework Programme: 241955 SYSCILIA
  • NIDDK NIH HHS: R01 DK065655
  • Foundation Fighting Blindness: C-CMM-0811-0547-RAD03
  • FAUN foundation:
  • Foundation Fighting Blindness: CMM-0811-0546-RAD02
  • Netherlands Organisation for Health Research and Development: E-rare grant 40-42900-98-1006
  • National Institutes of Health: NIH 2P30DK074038
  • Science Foundation Ireland: Principal Investigator SFI-11-1037
  • Technologiestichting STW: Vici-865.12.005
  • Seventh Framework Programme: 241955 SysCilia
  • NIDDK NIH HHS: P30 DK074038
  • Dutch Research Council (NWO): Veni-016.136.091
Open access
true
ISSN
1474-7596
Zeitschrift
Genome biology
Schlüsselwörter
  • Brain
  • Cerebellum
  • Retina
  • Cells, Cultured
  • Cilia
  • Microtubules
  • Animals
  • Mice, Inbred C57BL
  • Humans
  • Mice
  • Caenorhabditis elegans
  • Eye Abnormalities
  • Abnormalities, Multiple
  • ADP-Ribosylation Factors
  • Microtubule-Associated Proteins
  • Pedigree
  • Protein Binding
  • Mutation
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Male
  • Kidney Diseases, Cystic
  • Adenosine Triphosphatases
  • Exome
  • Basal Bodies
  • Katanin
Sprache
eng
Medium
Electronic
Online publication date
2015
Open access status
Open Access
Paginierung
293
Datum der Veröffentlichung
2015
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2015
Titel
KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
  • Research Support, N.I.H., Extramural
Ausgabe der Zeitschrift
16

Files

https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-015-0858-z https://europepmc.org/articles/PMC4699358?pdf=render

Datenquelle: Europe PubMed Central

Abstract
BACKGROUND: Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures. RESULTS: Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome. Patient-derived fibroblasts displayed reduced ciliogenesis potential and abnormally elongated cilia. Investigation of disease pathophysiology revealed that Kiaa0556 (-/-) null mice possess a Joubert syndrome-associated brain-restricted phenotype. Functional studies in Caenorhabditis elegans nematodes and cultured human cells support a conserved ciliary role for KIAA0556 linked to microtubule regulation. First, nematode KIAA0556 is expressed almost exclusively in ciliated cells, and the worm and human KIAA0556 proteins are enriched at the ciliary base. Second, C. elegans KIAA0056 regulates ciliary A-tubule number and genetically interacts with an ARL13B (JBTS8) orthologue to control cilium integrity. Third, human KIAA0556 binds to microtubules in vitro and appears to stabilise microtubule networks when overexpressed. Finally, human KIAA0556 biochemically interacts with ciliary proteins and p60/p80 katanins. The latter form a microtubule-severing enzyme complex that regulates microtubule dynamics as well as ciliary functions. CONCLUSIONS: We have identified KIAA0556 as a novel microtubule-associated ciliary base protein mutated in Joubert syndrome. Consistent with the mild patient phenotype, our nematode, mice and human cell data support the notion that KIAA0556 has a relatively subtle and variable cilia-related function, which we propose is related to microtubule regulation.
Date of acceptance
2015
Autoren
  • Anna AWM Sanders
  • Erik de Vrieze
  • Anas M Alazami
  • Fatema Alzahrani
  • Erik B Malarkey
  • Nasrin Sorusch
  • Lars Tebbe
  • Stefanie Kuhns
  • Teunis JP van Dam
  • Amal Alhashem
  • Brahim Tabarki
  • Qianhao Lu
  • Nils J Lambacher
  • Julie E Kennedy
  • Rachel V Bowie
  • Lisette Hetterschijt
  • Sylvia van Beersum
  • Jeroen van Reeuwijk
  • Karsten Boldt
  • Hannie Kremer
  • Robert A Kesterson
  • Dorota Monies
  • Mohamed Abouelhoda
  • Ronald Roepman
  • Martijn H Huynen
  • Marius Ueffing
  • Rob B Russell
  • Uwe Wolfrum
  • Bradley K Yoder
  • Erwin van Wijk
  • Fowzan S Alkuraya
  • Oliver E Blacque
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/26714646
DOI
10.1186/s13059-015-0858-z
eISSN
1474-760X
Externe Identifier
  • PubMed Central ID: PMC4699358
Funding acknowledgements
  • NIDDK NIH HHS: P30 DK074038
  • NIDDK NIH HHS: R01 DK065655
  • NIDDK NIH HHS: 2P30DK074038
Zeitschrift
Genome Biol
Schlüsselwörter
  • ADP-Ribosylation Factors
  • Abnormalities, Multiple
  • Adenosine Triphosphatases
  • Adult
  • Animals
  • Basal Bodies
  • Brain
  • Caenorhabditis elegans
  • Cells, Cultured
  • Cerebellum
  • Child
  • Child, Preschool
  • Cilia
  • Exome
  • Eye Abnormalities
  • Female
  • Humans
  • Katanin
  • Kidney Diseases, Cystic
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins
  • Microtubules
  • Mutation
  • Pedigree
  • Protein Binding
  • Retina
Sprache
eng
Country
England
Paginierung
293
PII
10.1186/s13059-015-0858-z
Datum der Veröffentlichung
2015
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2016
Titel
KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome.
Sub types
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
16

Datenquelle: PubMed

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