Essentially PROTEIN and GLYCANS.
Consist of a protein core which has one or more covalently attached glycosaminoglycan (GAG) chain(s).
Made by virtually all animal cells.
Huge functional diversity.
NB - Hyaluronan is not found covalently attached to proteoglycans but can non-covalently interact with proteoglycans.
PROTEOGLYCAN STRUCTURE = HIGH VARIABILITY
NB - heparin is a GAG which is a more highly sulphated analogue of HS found only in mast cells.
Membrane spanning - Syndecans.
GPI anchored - Glypicans.
Often extend from the cell surface into the ECM.
Functions mostly include cell signalling - modifying intracellular signalling pathways in response to extracellular ligands.
Other examples of cell membrane proteoglycans include neuropilin-1, NG2, betaglycan and CD44
Larger domain, site of GAG attachment and interacts with extracellular ligands.
Can be cleaved and shed into the extracellular matrix (ectodomains).
Short hydrophobic domain
Spans the plasma membrane.
Smaller than extracellular domain.
Attaches to the actin cytoskeleton and recruits intracellular signalling proteins in response to receptor oligomerisation / clustering.
GPI-anchored membrane protein.
Extracellular globular domain.
Can be shed into the extracellular environment. Largely through action of the extracellular lipase notum which cleaves the GPI anchor.
Heparan sulphate proteoglycans
Glypicans exclusively carry HS GAG chains.
Secreted into the extracellular matrix.
Key components of the extracellular matrix - many diverse structures and functions!
Large variety of molecules which can be loosely grouped into families. There are lots so pick your favourites....
Basement membrane proteoglycan, but also found in the interstitial matrix of some tissues.
Key component of vascular ECM.
Large multidomain core protein.
Predominantly has HS chains attached but CS chains can also be attached.
Can bind and crosslink many ECM and cell surface molecules. These interactions can be dependent upon or influenced by attached GAG chains, or the perlecan core protein can interact independently.
Theory that perlecan functions as an ECM scaffold linking the ECM to the cell surface.
Perlecan has functions in angiogenesis, chondrogenesis and endochondrial ossification.
Basal lamina proteoglycan.
Has HS chains attached.
Important in the development of the neuromuscular junction during embryogenesis.
Found in the basement membrane.
Carries HS chains, and is the only known collagen to carry HS chains.
HS chains aid binding of collagen XVIII to the basement membrane.
Has structural properties of both a collagen and a proteoglycan.
Important for blood vessel development in the eye.
C-terminal proteolytic cleavage yields endostatin which has been shown to be anti-angiogenic.
http://www.ncbi.nlm.nih.gov/books/NBK1900/ - whole text of essentials of glycobiology is available online!
(all websites accessed prior to 29/06/2012)
Couchman, J.R (2010) Transmembrane signalling proteoglycans. Annual review of cell and developmental biology. 26: 89-114
Dong, S (2002) Expression of collagen XVIII and localisatino of its GAG attachment sites. The journal of biological chemistry. 278: 1700-1707
Farach-Carson, MC (2007) Perlecan - a multifunctional extracellular proteoglycan scaffold. Glycobiology. 17(9):897-905
Fukai, N (2002) Lack of collagen XVIII/endostatin results in eye abnormalities. The EMBO journal. 21: (1535-1544)
Kiari, C (2002) Structure and function of aggrecan. Cell Res. 12(1): 19-32
Knox, S.M (2006) Perlecan: how does one molecule do so many things? Cellular and molecular sciences. 63(2):2435-2445
Perrimon, N (2001) Cellular functions of proteoglycans - an overview. Seminars in cell and developmental biology. 12: 65-67
Wight, TN (2002) Versican: a versatile extracellular matrix proteoglycan in cell biology. Curr opin cell biol. 14(5):617-623
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