Huang, Lijia, Szymanska, Katarzyna, Jensen, Victor L., Janecke, Andreas R., Innes, A. Micheil, Davis, Erica E., Frosk, Patrick ORCID: 0000-0002-9673-795X, Li, Chunmei, Willer, Jason R., Chodirker, Bernard N., Greenberg, Cheryl R., McLeod, D. Ross, Bernier, Francois P., Chudley, Albert E., Mueller, Thomas, Shboul, Mohammad, Logan, Clare V., Loucks, Catrina M., Beaulieu, Chandree L., Bowie, Rachel V., Bell, Sandra M., Adkins, Jonathan, Zuniga, Freddi I., Ross, Kevin D., Wang, Jian, Ban, Matthew R., Becker, Christian, Nuernberg, Peter, Douglas, Stuart, Craft, Cheryl M., Akimenko, Marie-Andree, Hegele, Robert A., Ober, Carole ORCID: 0000-0003-4626-9809, Utermann, Gerd, Bolz, Hanno J., Bulman, Dennis E., Katsanis, Nicholas ORCID: 0000-0002-2480-0171, Blacque, Oliver E., Doherty, Dan, Parboosingh, Jillian S., Leroux, Michel R., Johnson, Colin A. and Boycott, Kym M. (2011). TMEM237 Is Mutated in Individuals with a Joubert Syndrome Related Disorder and Expands the Role of the TMEM Family at the Ciliary Transition Zone. Am. J. Hum. Genet., 89 (6). S. 713 - 731. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

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Abstract

Joubert syndrome related disorders (JSRDs) have broad but variable phenotypic overlap with other ciliopathies. The molecular etiology of this overlap is unclear but probably arises from disrupting common functional module components within primary cilia. To identify additional module elements associated with JSRDs, we performed homozygosity mapping followed by next-generation sequencing (NGS) and uncovered mutations in TMEM237 (previously known as ALS2CR4). We show that loss of the mammalian TMEM237, which localizes to the ciliary transition zone (TZ), results in defective ciliogenesis and deregulation of Wnt signaling. Furthermore, disruption of Dania redo (zebrafish) tmem237 expression produces gastrulation defects consistent with ciliary dysfunction, and Caenorhabditis elegans jbts-14 genetically interacts with nphp-4, encoding another TZ protein, to control basal body-TZ anchoring to the membrane and cilio-genesis. Both mammalian and C. elegans TMEM237/JBTS-14 require RPGRIP1L/MKS5 for proper TZ localization, and we demonstrate additional functional interactions between C. elegans JBTS-14 and MKS-2/TMEM216, MKSR-1/B9D1, and MKSR-2/B9D2. Collectively, our findings integrate TMEM237/JBTS-14 in a complex interaction network of TZ-associated proteins and reveal a growing contribution of a TZ functional module to the spectrum of ciliopathy phenotypes.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Huang, LijiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szymanska, KatarzynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, Victor L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janecke, Andreas R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Innes, A. MicheilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davis, Erica E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frosk, PatrickUNSPECIFIEDorcid.org/0000-0002-9673-795XUNSPECIFIED
Li, ChunmeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willer, Jason R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chodirker, Bernard N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greenberg, Cheryl R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McLeod, D. RossUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernier, Francois P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chudley, Albert E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shboul, MohammadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Logan, Clare V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loucks, Catrina M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beaulieu, Chandree L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bowie, Rachel V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bell, Sandra M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adkins, JonathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zuniga, Freddi I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ross, Kevin D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, JianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ban, Matthew R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Douglas, StuartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Craft, Cheryl M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Akimenko, Marie-AndreeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hegele, Robert A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ober, CaroleUNSPECIFIEDorcid.org/0000-0003-4626-9809UNSPECIFIED
Utermann, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolz, Hanno J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bulman, Dennis E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Katsanis, NicholasUNSPECIFIEDorcid.org/0000-0002-2480-0171UNSPECIFIED
Blacque, Oliver E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doherty, DanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parboosingh, Jillian S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leroux, Michel R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, Colin A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boycott, Kym M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-483568
DOI: 10.1016/j.ajhg.2011.11.005
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 89
Number: 6
Page Range: S. 713 - 731
Date: 2011
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BARDET-BIEDL-SYNDROME; MECKEL-GRUBER-SYNDROME; BASAL BODY PROTEIN; PLANAR CELL POLARITY; OCULO-RENAL SYNDROME; CAENORHABDITIS-ELEGANS; CENTROSOMAL PROTEIN; ACTIN CYTOSKELETON; DISEASE GENES; MUTATIONSMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48356

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