Cell mutants defective in synthesizing a heparan sulfate proteoglycan with regions of defined monosaccharide sequence.
We have demonstrated that mouse LTA cells synthesize cell-surface heparan sulfate proteoglycans (HSPGs) with regions of defined monosaccharide sequence that specifically interact with antithrombin (HSPGact). It remains unclear how HSPGact can be generated by a biosynthetic pathway with no simple template for directing the ordered assembly of monosaccharide units. To examine this issue, we treated LTA cells with ethyl methanesulfonate and then isolated seven stable mutants that synthesize only 8-27% of the wild-type HSPGact but produce normal amounts of other HSPGs. These mutants are recessive in nature and fall into at least two different complementation groups. The delineation of the molecular basis of these defects should help to elucidate the manner by which cells synthesize HSPGs with regions of defined monosaccharide sequence.
De Agostini
A L
AL
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Lau
H K
HK
Leone
C
C
Youssoufian
H
H
Rosenberg
R D
RD
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D001665:Binding Sites; D002240:Carbohydrate Sequence; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002846:Chromatography, Affinity; D004187:Disaccharides / Q000302:isolation & purification; D005816:Genetic Complementation Test; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000302:isolation & purification; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation
D000991:Antithrombins; D011508:Chondroitin Sulfate Proteoglycans; D004187:Disaccharides; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate