Document Detail

Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein.
MedLine Citation:
PMID:  18826961     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-30
Journal Detail:
Title:  Human molecular genetics     Volume:  18     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-01-30     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  51-64     Citation Subset:  IM    
Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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MeSH Terms
Amino Acid Sequence
Cell Line
Extracellular Matrix Proteins / genetics,  metabolism
Eye Proteins / genetics,  metabolism
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, Wistar
Retina / metabolism
Sequence Alignment
Two-Hybrid System Techniques
Usher Syndromes / genetics,  metabolism*
Reg. No./Substance:
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

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