Heparan 2-O-sulfotransferase,hst-2, is essential for normal cell migration inCaenorhabditis 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.heparan sulfate ͉ proteoglycan

Syndecan regulates cell migration and axon guidance inC. elegans

“…A null mutation in the 2O-sulfotransferase hst-2 gene causes similar HSN migration defects, although they are less severe than those observed in sdn-1(zh20) animals ( Fig. 2E) (Bülow and Hobert, 2004;Kinnunen et al, 2005). By contrast, neither the 6O-sulfotransferase HST-6 nor the C5-epimerase HSE-5 is required for HSN migration (Bülow and Hobert, 2004), pointing to a crucial role of 2O-sulfated HS in this process.…”

Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: III. 2‐O‐sulfotransferase and C5‐epimerases

“…During larval development, expression is seen in the pharynx, muscle, and a subset of neurons (Kinnunen et al, 2005). HS2ST expression in the chick is seen throughout the embryo at stages 17-24, but expression is strongest in the pharyngeal arches and limb buds (Nogami et al, 2004).…”

“…RNAi of the Caenorhabditis elegans hst-2 gene, the C. elegans 2-OST orthologue, resulted in multiple phenotypic effects, including aberrant morphology and defects in egg laying (Turnbull et al, 2003). Several groups have begun to examine neuronal defects in hst-2 mutant worms (Bulow and Hobert, 2004;Kinnunen et al, 2005). Recently, a 2-OST in chicken was identified and found to be ubiquitously expressed throughout the chicken limb bud (Nogami et al, 2004).…”

The PAPS transporter PST-1 is required for heparan sulfation and is essential for viability and neural development inC. elegans

“…modifications in neural development (Bülow and Hobert, 2004;Kinnunen et al, 2005;Pratt et al, 2006). However, the function of PAPS transport and overall sulfation in development of the nervous system has not been investigated.…”