Cell interaction Flashcards
Fuction of selectins
Weak adhesion and rolling vs strong adhesion and emigration
Weak adhesion and rolling
- selectin-dependent
strong adhesion and emigration
- integrin dependent
Inflammation site
Endothelial cells express selectins,
oligosaccharides are located on lymphocytes
N-CAM
Neural cell adhesion molecules
fine tuning of interactions during development and regeneration
I-CAM
Intercellular adhesion molecules (I-CAM)
V-CAM
Vascular cell adhesion molecules (V-CAM)
Are cadherins and ig-like CAMs frequently expressed
yes coexpression often
integrins in procaryotes, plants or fungi
no
Caenorhabditis elegans integrins
two alpha subunits and one
beta subunit => form two integrins
vertebrates integrins
18 a subunits
and 8 b subunits
Integrins participate in (3)
- Cell-matrix adhesion
- Cell-cell adhesion
- Cell aggregation
Most integrins: connected via
intracellular anchor proteins to
actin (except: a6b4)
Integrin-Binding Sequences (on ECM proteins)
Involves frequently either D (Asp, aspartic acid) or E (Glu, glutamic acid) residue
RGD sequences
Arginine-Glycine-Aspartic acid
Collagen receptors
recognize ECM molecules
Leukocyte-specific receptors
recognize IG superfamily counter receptors
Integrin ligands often contain
… sites for receptor binding
accessory or ‘synergy
sites
Disintegrins can come from what animal
Large group of snake (viper) venom proteins containing a number of cysteine residues and RGD sequence
Disintegrins are rich with
RGB
What do Disintegrins do?
block the function of some integrins protein
Competitive inhibitor for integrin-fibrinin interactions and block blood coagulation
inhibitors of angionesis (blood vessel formation)
αIIbβ3 integrin mediates
blood platelet aggregation via binding to fibrinogen
integrin activation occurs via
exposure to Col IV or Thrombin (outside blood vessels)
Some integrins (α/β dimers) are
where are they
not constitutively active
– they are often on
the cell surface in inactive, non-ligand binding state
Activation can occur via (2)
extracellular ligand binding- outside-in” activation
Activation can occur from within the cell via the integrin cytoplasmic tail
Integrin activation is important for
cell aggregation (adhesion of circulating cells [platelets] to soluble matrix) cell-cell adhesion (leukocytes and inflammation)
Integrin activation – outside in is regulated by
extracellular ligand:
binding to the bent inactive conformation (weak interaction)
conformational change: straightening of alpha and beta chains
ligand will bind stronger
conformational change: separation of the cytoplasmic domains
Integrin activation – inside out is regulated by
seperation of the cytoplasmic domains is accompanied by conformational changes in them, allowing binding of the cytoplasmic proteins and signalling
separation of the cytoplasmic domains through talin and other activators would activated the head for ligand binding
Integrins affinity for their ligands
Integrins have low to moderate affinity for their ligands
clustering
Ligand binding promotes lateral diffusion and redistribution of integrins to focal complexes
soluble fibronectin dimers conformation?
is mediated by ?
-soluble fibronectin dimers have a compact conformation mediated by intramolecular interactions
Collagens are composed of
three polypeptide chains
- a-chains
46 collagen genes - 28 collagen types
What do collagens form? how can they exist?
triple helix
Exist as homotrimers or heterotrimers
structure of collagen alpha chain
GLY-X-Y
- X proline
- Y often hydroproline
- G glycine
What is at the center of the triple helix?
Glycine is every third reside, smallest aa
Collagen precursors
prepeptides and proalpha chains
How do collagen precursors become collagen (2)
hydroxylation, glycosylation
Glycosylation
monosaccharide galactose or disaccharide glycosylgalactose
Role of propeptide
guide intracellular formation of the triple-stranded collagen molecules
prevent intracellular formation of large collagen fibrils
When is the assembly of collagen occur?
only after secretion
Extracellular procollagen processing
- Only fibrillar collagens
uses
Procollagen N-proteinase Procollagen C-proteinase
and is zinc-dependent
Procollagen N-proteinase
ADAMTS-2-3-14
Procollagen C-proteinase
Tolloid Family
Both Procollagen C-proteinase and Procollagen N-proteinase are .. binding ..
zinc binding metalloproteases
removal of the C-propeptide
decreases critical concentration for self-assembly
Structure of a generic collagen fibril
- 300 nm in length
1000 amino acid residues
D period of collagen fibril
length of stagger between adjacent molecules
- D-periodic collagen fibril on the bottom with characteristic alternating light/dark pattern representing the gap and overlap fibril.
.. molecules form a microfibril in a … fashion
5 molecules form a microfibril in a concentric fashion
Formation of Fibrillar Collagens is an
entropy driven self-assembly process
After secretion in ER lumen what happens to prolines and lysines?
hydroxylated
prolyl hydroxylase have a cofactor of
vitamin C
prolyl hydroxylase characteristics
requires Fe+ and vitamin C
membrane bound
dioxygenase
inactivates the enzyme in absence of substrate
Scurvy
what is it? due to ?
defective collagen production
rupturting of blood vessels
defective wound healing
bleeding gums
Due to lack of Vitamin C (ascorbic acid)
– a cofactor for prolyl and lysyl hydroxylase
Cross-links in Collagens is due to
Lysyl Oxidase
Lysyl Oxidase are dependent on
copper-dependent
Lysyl Oxidase converts
some lysines and hydroxylsines to allysines and hydroxyl-allysines
covalent cross-links
Prolyl hydroxylase adds .. to … in .. dependent on ..
Prolyl hydroxylase - adds hydroxyl group to some prolines. (ER/Golgi) (Vitamin C and Fe2+)
Lysyl hydroxylase adds .. to … in .. dependent on ..
Lysyl hydroxylase - adds hydroxyl group to some lysines. (ER/Golgi) (Vitamin C and Fe2+)
N- and C-Propeptidases cleaves .. to … in .. dependent on ..
N- and C-Propeptidases - cleave collagen propeptides outside the cells. (Extracellular) (Zn2+)
Lysyl oxidase converts .. to … in .. dependent on ..
Lysyl oxidase - converts some lysines and hydroxylysines to allysines and hydroxy-allysines. These reactive aldehydes react with free (hydroxy)lysines to form covalent cross-links. (Extracellular) (Cu2+)
Collagen Defects syndrome
Ehlers-Danlos Syndrome
Types of Ehlers-Danlos Syndrome
Classical type (Collagen type V defect, a1 chain)
Hypermobility type (tenascin XB defect) (collagen fibrillogenesis)
Vascular type (Collagen type III)
Kyphoscoliosis type (Lysyl hydroxylase-1 deficiency)
Arthrochalasia type (Collagen type I)
Dermatosparaxis type (ADAMTS-2 defect)
