Heparan 2-O-sulfotransferase, hst-2, is essential for normal cell migration in Caenorhabditis elegans

Tarja Kinnunen, Zebo Huang, Joanne Townsend, Michelle M. Gatdula, Jillian R. Brown, Jeffrey D. Esko, Jeremy E. Turnbull

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The importance of heparan sulfate proteoglycans has been high-lighted 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.

Original languageEnglish
Pages (from-to)1507-1512
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number5
DOIs
Publication statusPublished - 1 Feb 2005
Externally publishedYes

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