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

doi:10.1073/pnas.0401591102

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

^*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, England; ^†School of Biological Sciences, University of Liverpool, Liverpool L69 72B, England; and ^¶Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093-0687

Edited by Barbara J. Meyer, University of California, Berkeley, CA (received for review March 5, 2004)

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.

Footnotes

↵ § To whom correspondence should be sent at the ‡ address. E-mail: t.k.kinnunen{at}liverpool.ac.uk.
↵ ‡ Present address: School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, England.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: DTC, distal tip cell; HS, heparan sulfate; HS2ST, heparan 2-O-sulfotransferase; HSN, hermaphrodite-specific neuron; HSPG, heparan sulfate proteoglycan; PAPS, 3′-phosphoadenosine 5′-phosphosulfate; RNAi, RNA interference.