proteoglycans

Definition: Proteoglycans are a class of glycoproteins that are heavily glycosylated. They consist of a core protein with one or more covalently attached glycosaminoglycan (GAG) chain(s). Proteoglycans are specialized glycoproteins with heterogeneous structures that are found in all connective tissues and on cell surfaces.

These glycosaminoglycan chains (GAGs) are long, linear carbohydrate polymers that are negatively charged under physiological conditions, due to the occurrence of sulfate and uronic acid groups.

Proteoglycans are named according to the structure of their principal repeating disaccharide. Some of the most common GAGs are heparan sulfate, chondroitin sulfate, and dermatan sulfate.

Proteoglycans and hyaluronic acid (HA, hyaluronan or hyaluronate) make up the third type of component in the extracellualr matrix (ECM), besides the fibrous structural proteins and cell adhesion proteins.

Structure

Proteoglycans consist of a core protein linked to one or more polysaccharides called glycosaminoglycans (GAGs).

Glycosaminoglycans are long repeating polymers of specific disaccharides in which one (or both) contains a sulfate residue. Proteoglycans are remarkable in their diversity. A specific ECM may contain several different core proteins, each containing different GAGs.

Types

Proteoglycans can be categorised depending upon the nature of their glycosaminoglycan chains :

 chondroitin sulfate
 dermatan sulfate
 keratan sulfate
 heparin
 heparan sulfate

Proteoglycans can also be categorised by size. Examples of large proteoglycans are aggrecan, the major proteoglycan in cartilage, and versican, present in many adult tissues including blood vessels and skin.

The small leucine rich repeat proteoglycans (SLRPs) include decorin, biglycan, fibromodulin and lumican.

Examples

 large proteoglycans

• aggrecan
• versican

 small leucine rich repeat proteoglycans (SLRPs)

• decorin
• biglycan
• fibromodulin
• lumican

Function

Membrane glycoproteins - Proteoglycans can also be integral membrane proteins and, through their binding to other proteins and fibroblast growth factor, act as modulators of cell growth and differentiation.

Extracellular matrix component - Proteoglycans are a major component of the extracellular matrix. They have diverse roles in regulating connective tissue structure and permeability. They form large complexes, both to other proteoglycans, to hyaluronan and to fibrous matrix proteins (such as collagen). They are also involved in binding cations (such as sodium, potassium and calcium) and water, and also regulating the movement of molecules through the matrix. Evidence also shows they can affect the activity and stability of proteins and signalling molecules within the matrix.

Individual functions of proteoglycans can be attributed to either the protein core or the attached GAG chain.

Biosynthesis and metabolism

The protein component of proteoglycans is synthesized by ribosomes and translocated into the lumen of the rough endoplasmic reticulum.

Glycosylation of the proteoglycan occurs in the Golgi apparatus in multiple enzymatic steps.

First a special link tetrasaccharide is attached to a serine side chain on the core protein to serve as a primer for polysaccharide growth. Then sugars are added one at the time by glycosyl transferase.

The completed proteoglycan is then exported in secretory vesicles to the extracellular matrix of the cell.

Types

 heparan sulphate proteoglycans
 basement membrane proteoglycans

Pathology

 proteoglycans defects

See also

 glycoproteins

References

 Hacker U, Nybakken K, Perrimon N. Heparan sulphate proteoglycans: the sweet side of development. Nat Rev Mol Cell Biol. 2005 Jul;6(7):530-41. PMID: 16072037

 Hebert DN, Garman SC, Molinari M. The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags. Trends Cell Biol. 2005 Jun 3; PMID: 15939591

 Selleck SB. Proteoglycans and pattern formation: sugar biochemistry meets developmental genetics. Trends Genet. 2000 May;16(5):206-12. PMID: 10782114