Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6968
pubmed:dateCreated
2003-12-19
pubmed:abstractText
Synthesis and sorting of lipids are essential for membrane biogenesis; however, the mechanisms underlying the transport of membrane lipids remain little understood. Ceramide is synthesized at the endoplasmic reticulum and translocated to the Golgi compartment for conversion to sphingomyelin. The main pathway of ceramide transport to the Golgi is genetically impaired in a mammalian mutant cell line, LY-A. Here we identify CERT as the factor defective in LY-A cells. CERT, which is identical to a splicing variant of Goodpasture antigen-binding protein, is a cytoplasmic protein with a phosphatidylinositol-4-monophosphate-binding (PtdIns4P) domain and a putative domain for catalysing lipid transfer. In vitro assays show that this lipid-transfer-catalysing domain specifically extracts ceramide from phospholipid bilayers. CERT expressed in LY-A cells has an amino acid substitution that destroys its PtdIns4P-binding activity, thereby impairing its Golgi-targeting function. We conclude that CERT mediates the intracellular trafficking of ceramide in a non-vesicular manner.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
426
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
803-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14685229-Alternative Splicing, pubmed-meshheading:14685229-Amino Acid Substitution, pubmed-meshheading:14685229-Animals, pubmed-meshheading:14685229-Binding Sites, pubmed-meshheading:14685229-Biological Transport, pubmed-meshheading:14685229-Cell Line, pubmed-meshheading:14685229-Ceramides, pubmed-meshheading:14685229-Cloning, Molecular, pubmed-meshheading:14685229-Cricetinae, pubmed-meshheading:14685229-Endoplasmic Reticulum, pubmed-meshheading:14685229-Genetic Complementation Test, pubmed-meshheading:14685229-Golgi Apparatus, pubmed-meshheading:14685229-Humans, pubmed-meshheading:14685229-Intracellular Membranes, pubmed-meshheading:14685229-Mutation, pubmed-meshheading:14685229-Phosphatidylinositol Phosphates, pubmed-meshheading:14685229-Protein Binding, pubmed-meshheading:14685229-Protein Structure, Tertiary, pubmed-meshheading:14685229-Protein-Serine-Threonine Kinases, pubmed-meshheading:14685229-Sphingomyelins
pubmed:year
2003
pubmed:articleTitle
Molecular machinery for non-vesicular trafficking of ceramide.
pubmed:affiliation
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. hanak@nih.go.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't