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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-2-7
pubmed:abstractText
During metazoan development, Wnt molecules are secreted from Wnt-producing cells, diffuse to target cells, and determine cell fates; therefore, Wnt secretion is tightly regulated. However, the molecular mechanisms controlling Wnt diffusion are not fully elucidated. The specific chondroitin sulfate (CS) structure synthesized by chondroitin-4-O-sulfotransferase-1 (C4ST-1) binds to Wnt-3a with high affinity (Nadanaka, S., Ishida, M., Ikegami, M., and Kitagawa, H. (2008) J. Biol. Chem. 283, 27333-27343). In this study we tested whether Wnt signaling regulates sulfation patterns of cell-associated CS chains by suppressing expression of C4ST-1 to trigger release of Wnt molecules from Wnt-producing cells. C4ST-1 expression was dramatically reduced in L cells that stably expressed Wnt-3a (L-Wnt-3a cells) and had CS with low affinity for Wnt-3a. Forced expression of C4ST-1 in L-Wnt-3a cells inhibited diffusion of Wnt-3a due to structural alterations in CS chains mediated by C4ST-1. Furthermore, sustained Wnt signaling negatively regulated C4ST-1 expression in a cell-autonomous and non-cell autonomous fashion. These results demonstrated that C4ST-1 is a key downstream target of Wnt signaling that regulates Wnt diffusion from Wnt-producing cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4199-208
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Down-regulation of chondroitin 4-O-sulfotransferase-1 by Wnt signaling triggers diffusion of Wnt-3a.
pubmed:affiliation
Department of Biochemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't