ECM Flashcards
Structural Proteins
Colalgen-strength
Elastin-resilience
Glycosaminoglycans
complex sugars that bind water and resist compression
Negatively charged
in joints/eye
Binds to proteoglycans
GAG
Proteoglycans
Proteints that vacantly bind to GAG
Adhesive glycoproteins
fibronectin, laminin, etactcin
Ground substance
Macromoleuclar compoentts-
structural proteins, glycosaminoglycans, proteoglycans, adhesive glycoproteins
Ground subtance+ cells
connective tissue
What is under the epithelium
basal lamina then connective tissue
Parenchyma
specialized epithelium
2 main regions of basal laminia + under that
=total is basement membrane
electron dense region underlying epithelial laer (rara/lucida/interna)-this part binds to hemidosmosomes
Much more electron dense under that-lamina densa
lamnia reticularis-made by fibroblasts, type 3 collagen
can only see difference in basement membrane with EM
under that is the stroma
what mediates continuum between cell surface and ecm
syndecans and integrins
Basement membrane
Basement membrane at EM and whats inside them
Can see with LM
Basal-laminin, fibronectin, coallagen, proteoglycans, enactin
Reticular-type 3 collagen (reticular fibers)
type 3 collagen is known as
reticular fibers
Stroma characteristic
fell cells, lots of matrix, dense irregular connective tissue
some tissues have specialized fibroblasts that secrete in stroma-secrete bone/cartledge
Collagen structure + facts
most abundant protein in body
individual collagen form triple helix, extensive, and can bind to other triple helixes to make huge molecule
Gly-x-y-gly-h atom (h is in middle of helix) side chain-repeats and fits inside helix
-X,Y s often P or K and can be hydroxylated-contributes to hydrogen binding or can be deaminited
K-contributes to cross linking to produce fibrils
mutation in glycine-disease
Fibril
Many triple helixes of collagen
Type 1, 2, 3 collagens
All form fibrils
1-bone , skin tendons-90% of body collagen
2-carledge
3-skin, blood vessels-exppand and contract-in stroma
type 7 collagen
anchors fibrils
beneath stratified squamous epithelia
stroma/blistering
collagen synthesis pathway
synthesized in city, bind SRP, ER, secreted
- hydroxlate some proteins and lysine
- glycoslate selected hydroxylysines
- extension peptides keep from multimerizing in cell-but does a little enough to be exerted through sec vesicle
- triplex forms-seceded out of cell as pro collagen
- made into tropocollagen by removing extension peptides
- self assemble into huge fibers
what hydroxylates glycine and prolines in collagen
vitamin c
can’t replace weak collagen with stronger-scurvy-teeth fall out
lysyl oxidase
cross-links tropocollagen molecules
DRAW SLIDE 10
Collagen type 3
Reticular-silver stain
in lymph nodes
more carbs thiner fibrils, more branches, fewer bundles
IMMUNE STRUCTURES
fibril associated collagen
ex-typle 9
interruption of triple helix-less rigid-form hinge
extensio peptides generally retained
Decorates outside of type 2 collagen (in cartilage)-9 is on outside
Join integrity
collagen type 4
network forming
major component of basement membrane+ basal lamina
extensio peptides are never cleaved-c and N termini interact=form dimer
N terminus has origination out of plane-vertical extensions-multilayer
- chicken wire array
- many of these form stacked network of sheets
Type 7 collagen
if mutated blistering-between epithelium and basement membrane
monomers make dimer, interact between stroma and lamina dense, keep storm attached to lamina densa
basement membrane NOT intact
BELOW LAMINA DENSA
type 12 collagen
transmembrane protein
anchors fibrils=monomers interact via c-terminal disulfide bonds-interacts with later densa
-N nd C not cleaved-interact to make anchoring fibrils
interacts with lamina densa
if this is messed up-blistering disease, epithelial cells peel away-basement membrane intact
ABOVE LAMINA DENSA
Mutants with shortened C-termini
cannot associate-blistering below BM
type 4 aka
lamina densa
Which collegians retain extension peptides during assembly
network forming
Which collagens form fibrils
1,2,3
which collagen stains dif and why
3 b/c increased CHO
elastin
highly cross linked monomers
- assembed extracellularly
- provide resillence
- elsatin fibers are surrounded by microfibrils composed of fibrilin
marfan sydnrome
mutation in fibrilin 1
overgrown lengthening of limbs
weak elastic fibers
distended aorta-prone to rupture
ECM disorders
- hyperextendable skin
- altered eslastin
- epidermolysis bullosa
- too much type 3 collagen-skin very stretchy
- no recoil
- epithelium and basement membrane peeled away
- type 7 collagen anchoring fibrils are disrupted
GAGs
glycosaminoglycans
negatively charged, bind to water, resist compression
molecules repel each her at negative charge, but attract water-fill a lot of space
can be sulfated or not sulfated + attached to protein or not
Aggrecan
aggrecan+type ii collagen+type 9+linker proteins
exist in chrdrocyte matrix-cartledge
Make up a lot of space
Forms aggregates with hylarunic acid
hyaluronic acid
gag that is non sulfated and not attached to protein
Perlecan-functions
basal laminae, strucural and filteing fucntion in basal lamina
Syndecan 1
fibroblast and epithelial cell surface
cell adhesion-co receptor
-bind to growth factors and present to dif receptors
connection between ECM and internal signaling pathway
Adhesive glycoproteins
attach to ECM, specific sequences-RGD, can interact with specific reports on cell (integrins)
laminas and fibronectins can bind many different molecules
has regions that bind to collagen/otehr components of ECM
Laminin’s and fibronectins
Integrin alpha6beta1
binds laminin
Laminin
major component of basal lamina
bind to cell surface receptors (integrins)-via RGD, type 4 collagen, and other adhesive proteins
Fibronectin
reduced in tumor cells-can allow uncontrolled growth
integrin alpha5 beta1-cell attachment site
two binding sites for interns, collagen, heparin, and fibrin
Modular domains
ECM componenets interacting
everyone interacts with everyone-bile network of different interactions depending on tissue type
Integrin binding
both to collagen and laminin
Are all gags bound to proteins?
no-hyalurnic acid is not
Lamin and fibronectin can only bind to oneanotehr molecome?
no-they have several modular domains
which collagens are found in ECM
aggrean, 2 , and 9
What is found in basement membrane
Perlecan (proteoglycan) and laminin
Integrins
Mediate communication between ECM and internal cell signaling by interacting with cytskeleton
dimers-not always active-help wbc/clots enter cell-would be bad if could enter whenever it wanted
both subunits involve din binding substrate via RGD sequences
beta subunts binds cytoskeleton (actin usually) that can initiate formation of signaling comeplexes
Focal adhesion complex
Acts with actin and itegrin to send signal into cell
integrins 2
Organize cytoskeleton-bind actin bdining proteins and the actin
focal accession forms at site of bounds intern via Rho GTPase
Recurits signalling moleculees
-focal adhesion kinase
Two transmembrane subunits
focal adhesion kinase
focadhesion kinase is signalling molecule that when active can phosphoryalte tyrosine residue-different signaling molecule form focal adhesion complex
-integrins active, assemble actin cytoskeleton, and organize signaling molecules
Major classes of interns
beta 1-bind ECM to fibronectin or laminin
beta 2-white blood cells
3-platelets
40desmosomes, bind specific laminin type
what are integrins important for
and what diseases are there
important for entry of abc into tissue, mediated by beta2
beta 2 mut in these leads to leukocyte adhesion deficeincy-no adhere to endothelium
beta 3 ingretins-glanzmans disease-inability to bind fibrinogen during clotting
Integrins and syndecans
cell membrane proteins that both interact with ECM components
intern with fibronectin-which is moldular-can bind other stuff like collagen/proteoglycans
interns can also bind to laminins along with syndecans
b1 integrins
b4 integrin
hemidesmosomes
just one of man systems involved in keeping epithelium bound to underlying tissue
mutation in beta 4-integrin can’t assemble-cant bind laminin 5 or collagen 12-epithelium peels away
pachorning filaments bind surface of epithelia to lamina dens
Intracellular signallinga nd integrins
Intergrin binding regulates intracellular signaling but other intracellular pathways can also regulate intern activity
things can go out to in and in to out
-done by conformational chages
integrin activation
something binds to signal receptor, receptor activates integrin through intracellular signaling events, integrin then binds to matrix
-activation is conformational change
-lymphocyte binding to endothelium (b2) and platelet bindign to fibrinogen (b3)
endothelium and platelet bindign to fibrinogen
(b2) and (b3)
lympho binding to endothelium via selectin
b2 integrin conormation changes allowing binding to endothelial surface receptors
during roll of lympho-integrins are activated-straighten up and spread out chains
selectins not only sow WBC down, but initiate signal needed to convert intern beta 2 on WBC to active, so can move into tissue
the integrins are on lympho
