title: Heparan 2-O-sulfotransferase, hst-2, is essential for normal cell migration in Caenorhabditis elegans.
abstract: The importance of heparan sulfate proteoglycans has been highlighted by a number of human genetic disorders associated with mutations in genes encoding for heparan sulfate proteoglycan protein cores or biosynthetic enzymes required for heparan sulfate (HS) assembly. To study the functional role of HS in Caenorhabditis elegans development cosmid sequence C34F6.4 was identified as the C. elegans ortholog of vertebrate heparan 2-O-sulfotransferase (HS2ST) and the gene named hst-2. HS2ST activity is present in C. elegans and is completely absent in a deletion mutant of hst-2, ok595, and specifically reduced by hst-2 RNA interference. Expression of hst-2 in CHO cells deficient in HS2ST rescues enzyme activity and binding of FGF2 to cell surface HS. hst-2 expression is found in the hypodermis, muscle, distal tip cells (DTCs), and in neurons. A null mutation in hst-2 causes cell migration defects. This work demonstrates sulfotransferase activity in C. elegans and indicates that specific 2-O-sulfate modifications are critical for normal HS functions in controlling cell migration.
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, England. t.k.kinnunen@liverpool.ac.uk
authors.forename: Tarja
authors.initials: T
authors.lastname: Kinnunen
authors.forename: Zebo
authors.initials: Z
authors.lastname: Huang
authors.forename: Joanne
authors.initials: J
authors.lastname: Townsend
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Gatdula
authors.forename: Jillian R
authors.initials: JR
authors.lastname: Brown
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Esko
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Turnbull
mesh_terms: D000818:Animals; D016466:CHO Cells; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D003001:Cloning, Molecular; D006224:Cricetinae; D005260:Female; D017353:Gene Deletion; D009154:Mutation; D010058:Oviposition; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D015238:Sulfotransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D011994:Recombinant Proteins; D015238:Sulfotransferases; C021350:heparitin sulfotransferase