Linked Life Data

20809529

Source:http://linkedlifedata.com/resource/pubmed/id/20809529

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-11-2
pubmed:abstractText
Retinoschisin (RS1) is a cell-surface adhesion molecule expressed by photoreceptor and bipolar cells of the retina. The 24-kDa protein encodes two conserved sequence motifs: the initial signal sequence targets the protein for secretion while the larger discoidin domain is implicated in cell adhesion. RS1 helps to maintain the structural organization of the retinal cell layers and promotes visual signal transduction. RS1 gene mutations cause X-linked retinoschisis disease (XLRS) in males, characterized by early-onset central vision loss. We analyzed the biochemical consequences of several RS1 signal-sequence mutants (c.1A>T, c.35T>A, c.38T>C, and c.52G>A) found in our subjects. Expression analysis in COS-7 cells demonstrates that these mutations affect RS1 biosynthesis and result in an RS1 null phenotype by several different mechanisms. By comparison, discoidin-domain mutations generally lead to nonfunctional conformational variants that remain trapped inside the cell. XLRS disease has a broad heterogeneity in general, but subjects with the RS1 null-protein signal-sequence mutations are on the more severe end of the clinical phenotype. Results from the signal-sequence mutants are discussed in the context of the discoidin-domain mutations, clinical phenotypes, genotype-phenotype correlations, and implications for RS1 gene replacement therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
This article is a US Government work and, as such, is in the public domain in the United States of America. Published in 2010 by Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1251-60
pubmed:dateRevised
2011-11-1
pubmed:meshHeading
pubmed-meshheading:20809529-Amino Acid Sequence, pubmed-meshheading:20809529-Amino Acid Substitution, pubmed-meshheading:20809529-Animals, pubmed-meshheading:20809529-Base Sequence, pubmed-meshheading:20809529-COS Cells, pubmed-meshheading:20809529-Cercopithecus aethiops, pubmed-meshheading:20809529-Codon, Initiator, pubmed-meshheading:20809529-Electroretinography, pubmed-meshheading:20809529-Exons, pubmed-meshheading:20809529-Eye Proteins, pubmed-meshheading:20809529-Gene Therapy, pubmed-meshheading:20809529-Genetic Association Studies, pubmed-meshheading:20809529-Humans, pubmed-meshheading:20809529-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:20809529-Introns, pubmed-meshheading:20809529-Male, pubmed-meshheading:20809529-Molecular Sequence Data, pubmed-meshheading:20809529-Point Mutation, pubmed-meshheading:20809529-Protein Folding, pubmed-meshheading:20809529-Protein Sorting Signals, pubmed-meshheading:20809529-Protein Structure, Tertiary, pubmed-meshheading:20809529-Recombinant Proteins, pubmed-meshheading:20809529-Retinoschisis
pubmed:year
2010
pubmed:articleTitle
Molecular mechanisms leading to null-protein product from retinoschisin (RS1) signal-sequence mutants in X-linked retinoschisis (XLRS) disease.
pubmed:affiliation
Section on Translational Research for Retinal and Macular Degeneration, National Institute on Deafness and Other Communication Disorders, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural