11 lectican family of proteoglycans
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51 Terms
What is a proteoglycan?
A core protein with one or more GAG chains attached
Approximately how many proteoglycan core proteins exist?
About 50
What are the two major locations of proteoglycans in tissues?
Cell surface and extracellular matrix
What anchors glypicans to the membrane?
A GPI anchor
What anchors syndecans to the membrane?
A type I transmembrane segment
Which GAG type is typical for glypicans and syndecans?
Heparan sulfate
Which GAGs can syndecans also carry in some contexts?
Chondroitin sulfate or dermatan sulfate
What are the two major families of CS DS KS proteoglycans?
Lecticans with link proteins and SLRPs
What is the repeating disaccharide of chondroitin sulfate?
Glucuronic acid and N acetylgalactosamine
What linkages connect CS disaccharides?
Beta 1-3 and beta 1-4
What is CSA type sulfation?
4 O sulfation on GalNAc
What is CSC type sulfation?
6 O sulfation on GalNAc
How is dermatan sulfate produced from CS?
By C5 epimerase converting GlcA to IdoA
What shared linker attaches CS DS and HS to core proteins?
Xyl Gal Gal GlcA tetrasaccharide linker
To which amino acid is the GAG linker attached?
Serine
What sugar addition commits a chain to CS DS synthesis?
Addition of GalNAc after the linker
What sugar addition commits a chain to HS synthesis?
Addition of GlcNAc after the linker
What is the activated sulfate donor used for sulfation?
PAPS
What are lecticans also called?
Hyalectans
Which lectican is the major cartilage proteoglycan?
Aggrecan
What GAG types does aggrecan carry?
Chondroitin sulfate and keratan sulfate
How many GAG chains can aggrecan carry approximately?
About 130
Which domains does aggrecan contain?
G1 G2 and G3
What does the G1 domain do?
Binds hyaluronan
What does the G3 domain do?
Binds proteins such as tenascins via its lectin like domain
What protein stabilises aggrecan binding to hyaluronan?
HAPLN1 cartilage link protein
What is the ternary complex in cartilage aggregates?
Hyaluronan aggrecan and link protein
What happens to hyaluronan conformation in cartilage aggregates?
It becomes extended and saturated with proteins
What physical effect explains cartilage swelling pressure?
The Donnan effect from fixed negative charges drawing in water
Why do sulfated GAG chains draw water into cartilage?
They attract counterions creating osmotic swelling pressure
How does cartilage handle compression during walking?
Water is squeezed out under load and returns when load is removed
What brain ECM structure uses HA and lecticans to regulate plasticity?
Perineuronal nets
Which lectican is a major component of perineuronal nets?
Aggrecan
How do perineuronal nets inhibit plasticity?
They act as hydrated barriers and sequester neurotrophic factors
How are HA chains attached at neuronal surfaces in nets?
Via HAS2 synthesis machinery rather than CD44
Which lectican is prominent in developing brain matrix?
Neurocan
Which lectican is prominent in adult brain matrix?
Brevican
Which tenascin is associated with early brain development?
Tenascin C
Which tenascin is associated with adult brain matrix?
Tenascin R
What are the oligomeric forms of tenascin C and R?
Tenascin C is a hexamer and tenascin R is a trimer
What do tenascins bind on lecticans?
The G3 domain
Why is aggrecan essential for skeletal development?
It forms cartilage matrix required as a template for bone growth
What is the nanomelic chicken mutation affecting?
Aggrecan leading to absent cartilage and lethal defects
Why do nanomelic chicks die at hatching?
They lack tracheal cartilage needed for breathing
What causes cartilage matrix deficiency CMD mouse phenotype?
A frameshift mutation in aggrecan preventing secretion
What causes brachymorphic mouse skeletal defects?
Mutation in PAPS synthase 2 causing undersulfated CS chains
What human disorder is linked to aggrecan haploinsufficiency?
Spondyloepiphyseal dysplasia Kimberley type
What is the inheritance pattern of Kimberley type spondyloepiphyseal dysplasia?
Autosomal dominant
Why can neurocan or brevican knockout mice appear normal?
Compensation by other lecticans and alternative crosslinkers
What compensatory crosslinking proteins can substitute for tenascins?
Fibulins such as fibulin 1 or 3
What is the main structural function shared by lecticans in cartilage and brain?
Providing hydration and forming extracellular matrix networks