Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans

Abstract

Glycosaminoglycans such as heparan sulphate and chondroitin sulphate are extracellular sugar chains involved in intercellular signalling. Disruptions of genes encoding enzymes that mediate glycosaminoglycan biosynthesis have severe consequences in Drosophila and mice. Mutations in the Drosophila gene sugarless, which encodes a UDP-glucose dehydrogenase, impairs developmental signalling through the Wnt family member Wingless, and signalling by the fibroblast growth factor and Hedgehog pathways. Heparan sulphate is involved in these pathways, but little is known about the involvement of chondroitin. Undersulphated and oversulphated chondroitin sulphate chains have been implicated in other biological processes, however, including adhesion of erythrocytes infected with malaria parasite to human placenta and regulation of neural development. To investigate chondroitin functions, we cloned a chondroitin synthase homologue of Caenorhabditis elegans and depleted expression of its product by RNA-mediated interference and deletion mutagenesis. Here we report that blocking chondroitin synthesis results in cytokinesis defects in early embryogenesis. Reversion of cytokinesis is often observed in chondroitin-depleted embryos, and cell division eventually stops, resulting in early embryonic death. Our findings show that chondroitin is required for embryonic cytokinesis and cell division.

Inhibiting Glycosaminoglycan Chain Polymerization Decreases the Inhibitory Activity of Astrocyte-Derived Chondroitin Sulfate Proteoglycans

“…CSPG GAG chains have been implicated in a variety of barrier-forming phenomena, including cell division (Mizuguchi et al, 2003), neural cell migration (Kubota et al, 1999;Perissinotto et al, 2000;Perris and Perissinotto, 2000), and inhibition of axon regeneration . cABC is effective at removal of GAG chains at the lesion site in vivo (McKeon et al, 1995;Moon et al, 2001;Bradbury et al, 2002), distal to the lesion site, when combined with a peripheral nerve graft (Houle et al, 2006), as well as in vitro.…”

“…Chondroitin sulfate proteoglycans (CSPGs) are a family of extracellular matrix (ECM) molecules with diverse functions in development (Bandtlow and Zimmermann, 2000;Schwartz and Domowicz, 2004), infection (Uyama et al, 2006), inflammation (Taylor and Gallo, 2006), and tissue morphogenesis and cell division (Mizuguchi et al, 2003). Of these, the role of CSPGs in mammalian CNS injury and plasticity has been the subject of intense investigation (Carulli et al, 2005).…”

Role of Glycosaminoglycans in Cellular Communication

“…Removal of chondroitin from the worm Caenorhabditis elegans, arrests embryogenesis preventing the transition from four cells to eight cells. 33 Removal of a single isoform of N-deacetylase/N-sulfotransferase results in lethality in mice at birth. 34 A failure of syndecan for a brief time in embryogenesis results in the absence of digits in the limbs of mice.…”

Structural and Functional Characterization of Oversulfated Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from the Notochord of Hagfish

“…We and others have shown the importance of this class of molecule, from simple chondroitin involved in cell division of a nematode (9) to differentially oversulfated CS-D and CS-E involved in neuroregulatory functions (10 -12) and the binding of growth factors in mammalian systems (13). While pursuing the critical structural elements in the CS variants, we became * This work was supported in part by the Science Research Promotion Fund of the Japan Private School Promotion Foundation and Grant-inaid for Exploratory Research 15659021 and the National Project on Functional Glycoconjugate Research Aimed at Developing New Industry of the Ministry of Education, Science, Sports, and Culture of Japan.…”