Proteoglycans: many forms and many functions

Abstract

Proteoglycans are produced by most eukaryotic cells and are versatile components of pericellular and extracellular matrices. They belong to many different protein families. Their functions vary from the physical effects of the proteoglycan aggrecan, which binds with link protein to hyaluronan to form multimolecular aggregates in cartilage; to the intercalated membrane protein CD44 that has a proteoglycan form and is a receptor and a cell-binding site for hyaluronan; to heparan sulfate proteoglycans of the syndecan and other families that provide matrix binding sites and cell-surface receptors for growth factors such as fibroblast growth factor (FGF). One feature that recurs in proteoglycan biology is that their structure is open to extensive modulation during cellular expression. Examples of protein changes are known, but a major source of structural variation is in the glycosaminoglycan chains. The number of chains and their length can vary, as well as their pattern of sulfation. This may result in the switching of different chain types with different properties, e.g., chondroitin sulfate and heparan sulfate, and it may also result in the selective expression of sulfated chain sequences that have specific functions. The control of glycosaminoglycan structure is not well understood, but it does appear to be used to change the properties of proteoglycans to suit different biological needs. Proteoglycan forms of proteins are thus important modifiers of the organization of the pericellular and extracellular matrices and modulators of the processes that occur there.

Immunohistochemical expression of heparan sulfate correlates with stromal cell proliferation in breast phyllodes tumors

“…For example, it regulates the activation of fibroblast growth factor receptors by fibroblast growth factors to elicit a series of downstream events, such as cell proliferation. [36][37][38] Several reports have suggested that alterations in the expression or biosynthesis of heparan sulfate are responsible for the differential affinities of fibroblast growth factor 1 and fibroblast growth factor 2 with their receptors, thus promoting breast cancer cell progression, metastasis and angiogenesis. [39][40][41] Hence, it is possible that heparan sulfate may manipulate the proliferative acitivity of the stroma in phyllodes tumors through the fibroblast growth factor/fibroblast growth factor receptor signalling pathways.…”

The Basic Science of Tendinopathy

“…Tendon contains a wide variety of proteoglycans, including the large aggregating proteoglycans and a variety of small leucine-rich proteoglycans (SLRPs) [116]. Proteoglycans and their constituent GAGs can influence many important physiological processes in tendon, including ion transport, water retention, the diffusion of nutrients, mediating cell-matrix interactions, resistance of compression and sequestration of growth factors and enzymes in the matrix [43,116]. Animal studies demonstrate biglycan may serve both a structural [109] and a signaling role [77] in developing tendon and biglycan and collagen VI are coexpressed in tendon development [61].…”

Intracellular trafficking of nonviral vectors

“…Sulfated proteoglycans consist of a core protein covalently linked to one or more sulfated glycosaminoglycans. 44 These highly anionic chains, which are among the most negatively charged components of the cell, are likely targets of nonviral assemblies carrying a net positive charge. Thus, by careful formulation of vector assembly, a positively charged complex may enable transfection through binding to these negatively charged moieties.…”