Extracellular Matrix Flashcards
1
Q
Why is the basement membrane considered an ECM?
A
- exterior to cells
- made by both epithelial and connective tissue
- main functions are communicating with cells and binding them to underlying connective tissue
2
Q
Describe some of the characteristics of ECM
A
- generally, medium is gel-like
- complex and intricate structural network that surrounds and supports cells within the connective tissue
- composed fibers (collagen/elastic), proteoglycans, proteins like laminin/fibronectin, GAG’s
3
Q
What allows for integrin and laminin to bind?
A
- this binding mediates the binding of the rest of the matrix
- integrins composed of alpha and beta structure
- dimer has binding site for amino acid motif RGD on outer membrane surface and binds to cytoskeleton on inner membrane surface
4
Q
Describe some characteristics of the interstitial matrix
A
- has cells scattered throughout
- cells are not connected to each other
- contains fibroblasts that have integrins, which bind with fibronectin, which in turn binds to proteoglycans and collagen
5
Q
fibronectin
A
- two chains linked via disulfide bridge
- contains several binding domains that interact with dif ECM molecules and integrin
- important in cell attachment to ECM
- in tissues, it forms fibers and aggregates
6
Q
fibrillar collagen
A
type I collagen
formed from braids of chains
7
Q
laminin
A
formed from three different protein chains
8
Q
tenascin
A
formed from six different protein chains
9
Q
type IV collagen
A
- long protein chain in kinks
- does not form fibers
10
Q
hyaluronan
A
- very long polysaccharide
- contains amino sugars (very unusual)
- also called glycosaminoglycan (GAG)
- no protein attached
- found outside animal tissue)
11
Q
decorin
A
- GAG chain and protein covalently attached
12
Q
perlecan
A
- present in cartilage almost exclusively
13
Q
aggrecan
A
- core protein of proteoglycan
- many chains attached
14
Q
Describe the EM of dense type I collagen ECM
A
- bundles of fibrils with striped pattern –> most prominent in type I collagen
- quasi-crystalline structure
- stain binds to different parts of the fiber in a regular fashion creating stripes
15
Q
Describe the assembly of type I collagen
A
- triple helices (tropocollagen aska collagen molecules)
- consists of two identical chains (both specified by same gene) and one dif chain (dif gene) - collagen molecules assemble into fibrils
- fibrils assemble into fibers
- depending on tissue type, fibers assemble into mesh (sometimes need strength in all directions) or in one direction (i.e. tendon)
16
Q
Describe EM of type I collagen fibers of cornea of eye
A
- fibrils lined up in sheet (viewed longitudinally)
- next layer has fibrils in cross section
- collagenous, densely packed tissue but still able to have light pass through it due to crystalline (para-crystalline) organization
17
Q
What is the importance of reticular connective tissue in the production of collagen?
A
- found in the lymph nodes and spleen
- makes type III collagen
- much finer fibrils that don’t assemble into fibers
- secreted by cell but don’t detach from cell (remain embedded)
- cells and fibers both make up a reticulum (network)
- creates storm for lymphocytes
18
Q
Name the most abundant protein in the animal kingdom
A
- type I collagen
- found almost everywhere in body (skin, tendon, bone, etc.)
- makes up about 40% of proteins in the body
19
Q
What are the minor collagens?
A
- types V-XII
- not very abundant but very significant when talking about collagen disorders
20
Q
Describe the cause of Classic Ehlers-Danlos syndrome (types I and II) and describe the symptoms
A
- due to mutations in COL5A1 and COL5A2 (mutation in type V collagen)
- causes hyper extension of joints and weakness of skin
21
Q
collagen disorders
A
- some caused by mutations
- when collagen assembles, covalent cross linked from prolines or lysine become hydroxylated by enzymes
- impaired hydroxylating enzymes forms weak collagen
- hydroxylating enzyme may require cofactor (vitamin C), without which proline will not be hydroxylated
- collagen made with pro-peptides that are removed, but impaired enzyme may not remove pro-peptide
22
Q
Describe EM of elastic connective tissue
A
- elastin can form sheets and fibers
- gives connective tissue a rubbery consistency
- found in organs that need to expand and snap back rapidly (i.e. aorta and other large blood vessels, Pina of ear, airways of lungs)
- tissues that make elastin also make fibrillin
23
Q
Describe mechanism of elastin
A
- unusual polypeptide backbone of elastin causes random coiling in normal, relaxed state
- stretching causes elastin molecules to straighten out, but still held to one another via cross-link
- removal of stretching force allows elastin molecules to coil again
24
Q
importance of fibrillin
A
- acts as a scaffold for elastin
- mutations in fibrillin gene lead to disruptions in elastin
25
Marfan syndrome
- caused by mutations in fibrillin gene
- absence of elastin-associated fibrillin mircrofibrils --> abnormal elastic tissue
- fibrillin acts as a repository for storage forms of growth factors
- microfibrils bind directly to cell through integrins
- in fibrillinopathies, integrin not binding microfibril, and growth factor goes unregulated
- causes compromise of mechanical interaction
26
fibronectin
- can bind to ECM or cell surface
- amino acid motif RGD to cell-binding domain
- heparan binding domain (ECM)
- collagen binding --> type I collagen
- regulatory factor for development and wound repair
27
proteoglycans
- consist of protein core and one or more covalently attached (O-linked) glycosaminoglycan (GAG) chains
- many straight chains of very long sugars with repeating monomers
- linked to membrane or embedded as integral membrane protein
- most are free in the ECM but various diseases result when proteoglycans prevented from binding to PM
28
glycoproteins
- proteins with carbohydrates attached (N-linked and O-linked)
- sugar chains are branched
i. e. fibronectin and laminin
29
common GAG's
- hyaluronan
- heparan sulfate
- chondroitin sulfate
- dermatan sulfate
30
Describe how cell-cell adhesions play a role in cancers and tumor invasion
- cells bind via non-junctional adhesions
| - cell binding is more transit and more temporary
31
What are the different junctional adhesion counterparts?
- focal contact (integrin binding to actin cytoskeleton) and adhesion belt (actin)
- hemi-desmosome (integral binding to intermediate filament) and desmosome (intermediate filament)
32
Describe function of basal lamina in kidney function
- epithelial tissue on either side with thick basal lamina between them
- found in filtration region of kidney
- involved in filtration
33
What composes the reticular lamina?
- reticular fibers (type III collagen)
- anchoring fibrils (type VII collagen)
- anchoring plaques (type IV collagen)
- very elaborate connections that create great structural integrity
34
role of adaptor proteins in integrin binding
- adaptor proteins bind to actin or intermediate filaments in cytoplasm of cell when extracellular matrix protein binds to integrin subunits in extracellular space
- nucleus can produce adaptor proteins that link to integrins on inside that help organized ECM
- matrix proteins can be dissolved, allowing cell to become motile
35
transmembrane co-localization of fibronectin fibers and actin filaments
- fibronectin fibers found on cell surface
- actin filaments found within cell
- by tracing fibers, see that there is tight coordination between extracellular and intracellular appendages
