The Glypicans: A family of GPI-anchored heparan sulfate proteoglycans with a potential role in the control of cell division

Abstract

The Glypican-related integral membrane proteoglycans (GRIPs) or Glypicans compose a distinctive, emerging family of heparan sulfate proteoglycans. The five known vertebrate glypicans include glypican (glypican-1), Cerebroglycan (glypican-2), OCI-5 (glypican-3), K-glypican (glypican-4) and glypican-5. The members of this family have similar core protein sizes (about 60 kDa), share a unique and very conserved cysteine spacing, and are linked to the cell membrane by a glycosyl phosphatidyl inositol (GPI)-anchor. All the structural features of the vertebrate glypicans are also represented in the product of dally (division abnormally delayed), a locus identified in Drosophila melanogaster. The dally mutants, the well established co-receptor activities of the cell surface proteoglycans for various ligands that are known to mediate developmental instructions, and the tissue and stage-specific expressions of the glypicans, all implicate the Glypican group of integral membrane proteoglycans in the control of cell division and patterning during development. This contention has recently been corroborated by identifying mutations in GPC3, the gene coding for the human homologue of OCI-5, that cause the Simpson-Golabi-Behmel syndrome, which is characterized by foetal and post-natal overgrowth, visceral and skeletal anomalies and a predisposition to the development of embryonal tumors.