Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2004-7-26
pubmed:abstractText
Polysialic acid (PSA) is a post-translational protein modification that is widely expressed among neural cell types during development. Found predominantly on the neural cell adhesion molecule (NCAM), PSA becomes restricted to regions of neurogenesis and neuroplasticity in the adult. In the mammalian genome, two polysialyltransferases termed ST8Sia-II and ST8Sia-IV have been hypothesized to be responsible for the production of PSA in vivo. Approaches to discover PSA function have involved the application of endoneuraminidase-N to remove PSA and genetic manipulations in the mouse to deplete either NCAM or ST8Sia-IV. Here we report the production and characterization of mice deficient in the ST8Sia-II polysialyltransferase. We observed alterations in brain PSA expression unlike those observed in mice lacking ST8Sia-IV. This included a PSA deficit in regions of neurogenesis but without changes in the frequency of mitotic neural progenitor cells. In further contrast with ST8Sia-IV deficiency, loss of ST8Sia-II did not impair hippocampal synaptic plasticity but instead resulted in the misguidance of infrapyramidal mossy fibers and the formation of ectopic synapses in the hippocampus. Consistent with studies of animal models bearing these morphological changes, ST8Sia-II-deficient mice exhibited higher exploratory drive and reduced behavioral responses to Pavlovian fear conditioning. PSA produced by the ST8Sia-II polysialyltransferase modifies memory and behavior processes that are distinct from the neural roles reported for ST8Sia-IV. This genetic partitioning of PSA formation engenders discrete neurological processes and reveals that this post-translational modification forms the predominant basis for the multiple functions attributed to the NCAM glycoprotein.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32603-13
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15140899-Animals, pubmed-meshheading:15140899-Axons, pubmed-meshheading:15140899-Behavior, Animal, pubmed-meshheading:15140899-Blotting, Western, pubmed-meshheading:15140899-Brain, pubmed-meshheading:15140899-Bromodeoxyuridine, pubmed-meshheading:15140899-Electrophysiology, pubmed-meshheading:15140899-Fear, pubmed-meshheading:15140899-Hippocampus, pubmed-meshheading:15140899-Homozygote, pubmed-meshheading:15140899-Hot Temperature, pubmed-meshheading:15140899-Male, pubmed-meshheading:15140899-Mice, pubmed-meshheading:15140899-Microscopy, Fluorescence, pubmed-meshheading:15140899-Models, Genetic, pubmed-meshheading:15140899-Mutagenesis, pubmed-meshheading:15140899-Mutagenesis, Site-Directed, pubmed-meshheading:15140899-Mutation, pubmed-meshheading:15140899-Neurons, pubmed-meshheading:15140899-RNA, pubmed-meshheading:15140899-Sialic Acids, pubmed-meshheading:15140899-Sialyltransferases, pubmed-meshheading:15140899-Synapses, pubmed-meshheading:15140899-Time Factors, pubmed-meshheading:15140899-Water
pubmed:year
2004
pubmed:articleTitle
Sialyltransferase ST8Sia-II assembles a subset of polysialic acid that directs hippocampal axonal targeting and promotes fear behavior.
pubmed:affiliation
Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't