Topic 6: ECM and Integrins Flashcards
what are the main classes of the ECM?
- Basal Lamina
- connective tissue
what is the ECM made from?
network of polysaccharides and proteins secreted by cells and embed other cells
what is the function of the ECM?
- hold the shape of cell and mechanical properties
- holds cells and tissues together
what is the function of connective tissue?
to support the structure of the body
what are the 4 functions of the basal lamina?
- filters what comes form epithelial cells and goes to the connective tissue
- scaffold for the regenerating cells
- support to overlying epithelium or endothelium
- guide cells for embryonic development
what is the Basal lamina?
aka the basement membrane
a thin sheet of extracellular matrix that separates the epithelial cells and the connective tissue and provides a connection between them
(under the epithelial cells)
kind of a filter between them
what is connective tissue made from?
made from fibers and proteins to create a framework and support structure for body tissues and organs
- majority of the ECM volume in connective tissue is secreted by fibroblasts cells
what are the 2 types of specialized connective tissue?
bones and cartilage
what are the 3 types (classes) of molecules in the ECM?
- proteoglycans
- structural proteins
- adhesive glycoproteins
what is GAG and what is the usual animo acid it contains?
a unbranded chain of alternating polysaccharides of an animo sugar and uric acid that are both usually sulphated
N-acetylglucoamine or N-acetygalatosmine
what is proteoglycan?
is it a group of glycoproteins that contain a one or more of the core protein glycosaminoglycan (GAG)
an example of proteoglycan?
perlecan
what is the characteristics of GAG?
- highly charged
- very hydrophilic
- fills up most of the extracelluar space
- attracts water and cation to create gel for collagen to get stuck in
- water in it makes it withstand compressive forces
what are the 4 types of GAGs and which is the simplest?
- hyaluronan (simplest)
- heparin sulfate
- chondroitin sulphate
- keratan sulfate
describe hyaluronan and the characteristics
- D- glucuronic acid
- N-acetyl-D- glucosamine
B(1-3) linkage - simplest
- not sulphated
- not linked to any core protien
describe chondroitin (or dermatan)
- D-glucuronic acid/L-iduronic acid
- N-acetyl-D-galactosamine
a/B(1-3) linkage - O linked
describe heparin sulfate
- D-glucuronic acid/L-iduronic acid
- N-acetyl/N-sulfo -D-glusamine
a/B(1-4) linkage - O- linked
describe keratan sulfate
- D-galactose
- N-acteyl-D-glucoamine
B(1-4) linkage - N-linked
what is the difference between proteoglycans and other glycoproteins
- at least one of the sugars in a glycoprotein have to be a GAG
- the long chain if unbranched GAG can comprise most of the weight of the molecule
- they are very diverse
what is aggrecan?
it is a major component of cartilage
- its backbone is mostly made up of hyaluronan and can be modified by GAG
- gel like properties
- attaches toothed aggrecan non covalently
what is the function of proteoglycan and what does it bind to?
- bind to other matrix proteins like collagen and adhesive glycoproteins
- regulate the activity of secreted signalling proteins by functioning as a cell surface co receptor
what are the types of structural protein
collagen
elastins
what is collagen?
the most abundant protein in mammals (25%) used as structure for cells
what are the important types of collagen (where are they found?)
type 1 - skin, tendons and internal organs
type 4- basal lamina
type 9 & 12 - cartilage
describe the structure and function of Type 1 collagen
- long strong fibers with huge TENSILE STRENGH to withstand the force of the bones
- construction of bone (30%)
- secreted by fibroblast in connective tissue
describe the structure and function of Type 4 collagen
form a branching network that is founding he basal lamina
what types of collagen help co assemble type 1 collagen
Type 5 and 9 (minor fibrillar collagens)
describe the structure and function of Type 9 and 12 collagen
in cartilage, they are covalently bound at regular intervals along the type 2 fibrils to allow them to be more loosely associated to the cartilage
what is the formation of collagen fibril
1) synthesis of individual alpha chain in the pro peptides in the rough ER
2) the pro peptides associate to form trimers and selected proline and lysine residues get hydroxylated
3) those modifications allow trimer formation and the being of chaperone Hsp47
4-6) secretion of the pro peptidase
7) the N & C terminus are cleaved by extracelluar proteases
8) the trimers get staggered by 67 nm in fibrils and covalently cross linked
what is elastin?
it forms the elastic fibers in the ECM to give the tissue strechness (skin, blood vessels & lung)
- very hydrophobic
what are adhesive glycoproteins and where are they found? (examples)
they are proteins that anchor cells to the basal lamina
eg. laminin and fibronectin
explain laminin function
it is the main adhesive glycoprotein and is the ligand that binds the basal lamina to integrins
explain fibronectin function
an adhesive glycoprotein that helps organize and attach cells to the matrix
how does fibronectin attach cells to the matrix?
it binds collagen and herapan sulfate and to the cell adhesion receptor called integrins
each specific integrin can influences the shape, movement and underlying cytoskeleton of the cell
how is fibronectin turn into fibrils produced and travel?
the dimeric forms are produced by cells and circulate in the blood
the are turning into fibrils on the surface of cells when they bind to integrins. This is because the integrin are attached to actin filaments so this causes a stretch in the firbonectin and exposes the site for more integrins to bind turning into more fibrils
what are the 2 main type of connection inetgrin make with cytoskeletons?
focal adhesion: linked to actin filaments (stress fibers)
hemisomes - linked to intermediate filaments
what is the structure of inetgrin?
they are transmembrane heterodimer composed of alpha and beta subunit
a mixmatch of 8 types of beta subunits and 18 alpha subunits
what’s the difference between beta1 and beta2 sub its of integrins?
beta 1 is found on the surface of vetebraes cells
beta 2 is found on the surface of white blood cell
what is the function of integrins?
bind the ECM proteins in animal cells
how do integrins get activated?
by allosteric regulation causing inside out and outside in signalling
what are inside out signalling
comes from intracellular signal changing the conformation of the inetgrin to extended close it does this by talon opening and attaching to the integrin along with kindling and RIAM.
what is outside in signalling?
after inside our signalling, the integrin binds to the ECM and the attcahment to he cytoskeleton drives the integrins to the extended open confirmation which causes vinculin to bind to the talin and bind to the actin filament
how does mechanical force affect cell matrix adhesion?
it opens up the talin to allow vindullin to bind
why is cell attachment needed?
cell proliferation and survival
