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The Elusive Functions of Proteoglycans

Year: 2000
Type: review
Abstract: Proteoglycans: cell biologists have had a love-hate relationship with these molecules almost since their discovery.Their biochemical properties, dominated by heterogeneous and highly charged glycosaminoglycan (GAG) 1 chains, can make purification challenging and structural analysis painful.Their ability to bind scores of growth factors, growth factor-binding proteins, extracellular proteases, protease inhibitors, extracellular matrix molecules, and other proteins takes the concept of molecular promiscuity to new heights.On top of this, they seem always to be underfoot, showing up on plasma membranes in hundreds of thousands of copies per cell and in extracellular matrices at milligram per milliliter concentrations.And yet despite these peculiarities (or perhaps because of them) proteoglycans have inspired an extraordinary range of models, theories, and speculation.Since the 1960s, proteoglycans have been credited, in one system or another, with controlling the following: cell division, adhesion, spreading, migration, chemoattraction, axon guidance, matrix assembly, lipoprotein uptake, extracellular proteolysis, and viral entry.Do proteoglycans do all of these things?Progress on this question during the past decade has been recently kicked into high gear by a flurry of in vivo results (in mice, frogs, flies, and worms), in many cases coming from investigators who never intended to become involved with such difficult molecules.Here, we review some of these findings and discuss how they both confirm old notions of proteoglycan function and suggest new ones.We have chosen to focus exclusively on the heparan sulfate proteoglycans (HSPGs), in part because new data on these molecules have been particularly plentiful, but mostly because those data speak more directly about the functions of GAGs, the moieties that make proteoglycans unique.However, it should be noted that in vivo studies of proteoglycans that primarily bear chondroitin/dermatan sulfate and keratan sulfate (the other families of GAG) are also providing important new insights (Fässler et al., 1994;
Language: English
Subfield: Cell Biology
Open Access status: green
OpenAlex ID: W2166363199
FWCI: 2.284
Cites: 59
Cited by: 256
Related to: 10