| Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein. | |
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MedLine Citation:
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PMID: 18826961 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Usher syndrome (USH) and Leber congenital amaurosis (LCA) are autosomal recessive disorders resulting in syndromic and non-syndromic forms of blindness. In order to gain insight into the pathogenic mechanisms underlying retinal degeneration, we searched for interacting proteins of USH2A isoform B (USH2A(isoB)) and the LCA5-encoded protein lebercilin. We identified a novel isoform of the centrosomal ninein-like protein, hereby named Nlp isoform B (Nlp(isoB)), as a common interactor. Although we identified the capacity of this protein to bind calcium with one of its three EF-hand domains, the interacton with USH2A(isoB) did not depend on this. Upon expression in ARPE-19 cells, recombinant Nlp(isoB), lebercilin and USH2A(isoB) were all found to co-localize at the centrosomes. Staining of retinal sections with specific antibodies against all three proteins revealed their co-localization at the basal bodies of the photoreceptor-connecting cilia. Based on this subcellular localization and the nature of their previously identified binding partners, we hypothesize that the pathogenic mechanisms for LCA and USH show significant overlap and involve defects in ciliogenesis, cilia maintenance and intraflagellar and/or microtubule-based transport. The direct association of Nlp(isoB) with USH2A(isoB) and lebercilin indicates that Nlp can be considered as a novel candidate gene for USH, LCA and allied retinal ciliopathies. |
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Authors:
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Erwin van Wijk; Ferry F J Kersten; Aileen Kartono; Dorus A Mans; Kim Brandwijk; Stef J F Letteboer; Theo A Peters; Tina Märker; Xiumin Yan; Cor W R J Cremers; Frans P M Cremers; Uwe Wolfrum; Ronald Roepman; Hannie Kremer |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-09-30 |
Journal Detail:
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Title: Human molecular genetics Volume: 18 ISSN: 1460-2083 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-16 Completed Date: 2009-01-30 Revised Date: 2012-03-12 |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: England |
Other Details:
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Languages: eng Pagination: 51-64 Citation Subset: IM |
Affiliation:
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Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Cell Line Extracellular Matrix Proteins / genetics, metabolism Eye Proteins / genetics, metabolism Humans Mice Mice, Inbred C57BL Microtubule-Associated Proteins / chemistry, genetics, metabolism* Molecular Sequence Data Nuclear Proteins / chemistry, genetics, metabolism* Optic Atrophy, Hereditary, Leber / genetics, metabolism* Photoreceptor Cells / metabolism Protein Binding Protein Isoforms / genetics, metabolism Rats Rats, Wistar Retina / metabolism Sequence Alignment Two-Hybrid System Techniques Usher Syndromes / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Extracellular Matrix Proteins; 0/Eye Proteins; 0/Microtubule-Associated Proteins; 0/NIp protein, human; 0/Nuclear Proteins; 0/Protein Isoforms; 0/USH2A protein, human; 0/lebercilin protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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