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

Publisher Website
Google Scholar
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 inCaenorhabditis elegansdevelopment cosmid sequence C34F6.4 was identified as theC. elegansortholog of vertebrate heparan 2-O-sulfotransferase (HS2ST) and the gene namedhst-2. HS2ST activity is present inC. elegansand is completely absent in a deletion mutant ofhst-2,ok595, and specifically reduced byhst-2RNA interference. Expression ofhst-2in CHO cells deficient in HS2ST rescues enzyme activity and binding of FGF2 to cell surface HS.hst-2expression is found in the hypodermis, muscle, distal tip cells (DTCs), and in neurons. A null mutation inhst-2causes cell migration defects. This work demonstrates sulfotransferase activity inC. elegansand indicates that specific 2-O-sulfate modifications are critical for normal HS functions in controlling cell migration.