Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-6-1
pubmed:abstractText
Juvenile neuronal ceroid lipofuscinosis (JNCL), Batten disease, is an autosomal recessive lysosomal storage disease associated with mutations in CLN3. CLN3 has no known homology to other proteins and a function has not yet been described. The predominant mutation in CLN3 is a 1.02 kb genomic deletion that accounts for nearly 85% of the disease alleles. In this mutation, truncation of the protein by a premature stop codon results in the classical phenotype. Additional missense and nonsense mutations have been described. Some missense substitutions result in a protracted phenotype, with delays in the onset of classical clinical features, whereas others lead to classical JNCL. In this study, we examined the effect of naturally occurring point mutations on the intracellular localization of CLN3 and their ability to complement the CLN3-deficient yeast, btn1-Delta. We also examined a putative farnesylation motif thought to be involved in CLN3 trafficking. All of the point mutations, like wild-type CLN3, were highly associated with lysosome-associated membrane protein II in non-neuronal cells and with synaptophysin in neuronal cell lines. In the yeast functional assay, point mutations correlating with a mild phenotype also demonstrated CLN3 activity, whereas the mutations associated with severe disease failed to restore CLN3 function completely. CLN3 with a mutation in the farnesylation motif trafficked normally but was functionally impaired. These data suggest that these clinically relevant point mutations, causative of Batten disease, do not affect protein trafficking but rather exert their effects by impairing protein function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
735-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10749980-Amino Acid Motifs, pubmed-meshheading:10749980-Amino Acid Sequence, pubmed-meshheading:10749980-Base Sequence, pubmed-meshheading:10749980-Cell Line, pubmed-meshheading:10749980-Cyclins, pubmed-meshheading:10749980-DNA, pubmed-meshheading:10749980-Fungal Proteins, pubmed-meshheading:10749980-Humans, pubmed-meshheading:10749980-Immunohistochemistry, pubmed-meshheading:10749980-Membrane Glycoproteins, pubmed-meshheading:10749980-Molecular Chaperones, pubmed-meshheading:10749980-Molecular Sequence Data, pubmed-meshheading:10749980-Mutation, Missense, pubmed-meshheading:10749980-Neuronal Ceroid-Lipofuscinoses, pubmed-meshheading:10749980-Saccharomyces cerevisiae, pubmed-meshheading:10749980-Saccharomyces cerevisiae Proteins, pubmed-meshheading:10749980-Synaptophysin
pubmed:year
2000
pubmed:articleTitle
Batten disease: evaluation of CLN3 mutations on protein localization and function.
pubmed:affiliation
Program in Gene Therapy, Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't