Proteoglycans and pattern formation: sugar biochemistry meets developmental genetics.
While it has been long appreciated that sugar-modified proteins coat the cell surface, their functions are poorly understood. Here, I describe recent genetic studies that demonstrate that one class of sugar-modified proteins, cell-surface proteoglycans, play crucial roles in morphogenesis, growth regulation and tumor suppression. Mutations that affect individual proteoglycans or the enzymes required for glycosaminoglycan synthesis regulate Wingless and Decapentaplegic signaling in Drosophila, and body size in mice and humans. Compromising proteoglycan function is also associated with the development of Wilm's tumors and hereditary multiple exostoses. In this review, these biological findings are placed in the context of proteoglycan biochemistry and molecular function.
Selleck
S B
SB
Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA. selleck@u.arizona.edu
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D029721:Drosophila Proteins; D006025:Glycosaminoglycans / Q000096:biosynthesis* / Q000235:genetics; D006133:Growth Substances / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D009396:Wilms Tumor / Q000378:metabolism; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D006025:Glycosaminoglycans; D006133:Growth Substances; D006497:Heparan Sulfate; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C098128:dally protein, Drosophila; C064196:dpp protein, Drosophila; C074622:wg protein, Drosophila