BIOB10H3 Lecture Notes - Lecture 11: Occludin, Intermediate Filament, Endothelium
25 Jun 2018
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Lecture 11: Extracellular Matrix
Extracellular Matrix (ECM)
Everything that surrounds the cells (made by cells)
oE.g. red blood cells ECM is plasma
Functions:
for support of cells/tissues
signals to cells:
osends survival signals, signals to migrate, etc.
ogive cells “identity”
site of cell attachment
substrate for cells to migrate over
Matrix - network of interacting components
ECM - a mesh of fibrous proteins secreted by cells
includes bone, blood, tendons, cartilage connective tissue and basement membranes
Cells: fibroblast, osteoblasts, chondroblasts, etc. cells with “blast” can make ECM
ECM Proteins
1. Collagen
2. Laminin
3. Fibronectin
4. Proteoglycan - protein + polysaccharide
Polysaccharide - called GAGs
oe.g. Hyaluronic acid (HA)
ocharged molecules that bind water
different ECM’s have different amounts of ECM proteins depending on function
oamount of water varies (blood versus bone)
oamount of bound mineral varies
e.g. Bone has Type I Collagen that binds calcium phosphate
“calcified matrix”
find more resources at oneclass.com
find more resources at oneclass.com
calcium stored in bone, also gives bone its dense, supporting role as the skeleton
ECM Proteins: Collagen
most common ECM protein 19 genes
most abundant protein in animal kingdom
a secreted, fibrous glycoprotein
secreted by fibroblasts, osteoblasts, smooth muscle and epithelial cells
trimers which wind around each other in a triple helix (homotrimers or heterotrimers)
provide high tensile strength
continuously being remodeled
degradation and reconstruction
accomplished by secretion of matrix metalloproteinases (MMP’s)
oenzyme that hydrolyze matrix proteins
or secretion of lysosomes
oe.g. By osteoclasts which degrade the bone matrix
ECM “Beauty” & Therapeutic Treatments
Beauty Industry
oinject ECM components (collagen, HA)
o“filler” products to lessen wrinkles, accentuate features
oreplace ‘old’ ECM with ECM of babies (HA) more water-bound ECM therefore less wrinkles
otransient effect due to immune clearance
Joint repair
oECM as diet supplements
e.g. Glucosamine (GAG precursor) for arthritis
oingest and replace ECM
owill it target correctly or get broken down?
Integrins: Major ECM Receptor
integral plasma membrane protein
main cell protein which binds to ECM
obinds to RGD sequence on ECM proteins
heterodimer with an and subunit
many types of each over 20 different combinations
Integrins: “Inside-out Activation”
1. to bind to ECM, integrins must first be ‘activated’
2. conformational change induced by talin binding to cytosolic tail
find more resources at oneclass.com
find more resources at oneclass.com
Can experimentally block binding to ECM by adding synthetic RGD peptides
owill compete with ECM for integrin binding
oused therapeutically to prevent clot formation
Integrins
important for adhesion to ECM or other cells
transmit external signals intracellularly
A. Adhesion - integrin binds to tripeptide RGD sequence in fibronectin, laminin, proteoglycans and
collagen
o2 Types of Adhesion complexes
1. Focal Adhesions - integrins link ECM (outside) to F-actin & myosin network (cytosolic
side)
Actin/myosin forces within focal adhesions provide traction forces (i.e. during
cell migration)
2. Hemi-desmosome (half-desmosome)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Everything that surrounds the cells (made by cells: e. g. red blood cells ecm is plasma. Functions: for support of cells/tissues signals to cells: sends survival signals, signals to migrate, etc, give cells identity site of cell attachment substrate for cells to migrate over. Ecm - a mesh of fibrous proteins secreted by cells includes bone, blood, tendons, cartilage connective tissue and basement membranes. Calcified matrix calcium stored in bone, also gives bone its dense, supporting role as the skeleton. Most common ecm protein 19 genes. Beauty industry: inject ecm components (collagen, ha, filler products to lessen wrinkles, accentuate features, replace old" ecm with ecm of babies (ha) more water-bound ecm therefore less wrinkles, transient effect due to immune clearance. Integrins: major ecm receptor integral plasma membrane protein. Main cell protein which binds to ecm: binds to rgd sequence on ecm proteins heterodimer with an and subunit. Many types of each over 20 different combinations.
