Difference between revisions of "Talk:2009 Lecture 13"

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(New page: ANAT3231 - Cell Biology
Lecture 12 and 13
School of Medical Sciences
The University of New South Wales Dr Mark Hill Cell Biology Laboratory Room G20 Wallace Wurth Building Email: m.h...)
 
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Degrade proteoglycan (aggrecan)
 
Degrade proteoglycan (aggrecan)
 
Also a mouse model generates antibodies to proteogycan
 
Also a mouse model generates antibodies to proteogycan
Cell Adhesion to ECM
 
Direct linkage to collagen or proteoglycan
 
insertion of fibers into membrane
 
covalent attachment to membrane lipid
 
Linking glycoproteins
 
fibronectin
 
laminin
 
Fibronectin Structure
 
Fibronectin Structure
 
dimer connected at C-terminal
 
S-S linkages
 
rigid and flexible domains
 
cell binding segment RGDS
 
arg-gly-asp-ser
 
binds receptor in membrane
 
domains bind
 
heparin sulphate
 
Collagen
 
hyaluronic acid
 
Gangliosides
 
fibronectin
 
Fibronectin Function
 
cell adhesion
 
migration pathways
 
blocking fibronectin with antibody
 
prevents neural crest migration
 
extension of axons and dendrites
 
branching
 
Differentiation
 
basal laminae
 
under skin and between organs
 
blood
 
clotting process, link to fibrin
 
Laminin
 
Laminin Structure
 
Laminin Structure
 
cross-shaped glycoprotein
 
3 polypeptides a, b1, b2
 
carbohydrate (13% by weight)
 
Mr 900K
 
separate binding domains
 
collagen IV
 
heparin
 
heparin sulphate
 
cell binding
 
cell specific binding
 
liver, nerve
 
cell surface receptor
 
Laminin Function
 
cell adhesion
 
migration pathways
 
stimulates growth of axons
 
development and regeneration
 
differentiation
 
basal laminae
 
most abundant linking glycoprotein
 
Integrin- Structure
 
Integrin Function
 
cell membrane receptor for ECM linkers
 
binds RGDS motif
 
2 subunits alpha (α) and beta (β)
 
transmembrane
 
linked to cell cytoskeleton actin microfilaments
 
via talin and vinculin
 
focal contacts
 
For Review see
 
Integrin signaling revisited. Schwartz MA.Trends Cell Biol 2001 Dec;11(12):466-70
 
Focal Adhesions- Microfilaments
 
Cell signalling
 
Modify cell cytoskeleton
 
Activate intracellular signalling pathways
 
Cell motility
 
Integrin- Function
 
Activate members of  Rho-family of small GTPases
 
Conversely, Rho- and Ras-family proteins can influence the ability of integrins to bind their ligands
 
control of cell motility, and therefore on invasive and metastatic behavior
 
Integrin binding ECM has effects on cell survival, particularly for cells of epithelial origin
 
specific integrins have selective effects on efficiency of signal transduction in cell survival pathways
 
Text modified from: New aspects of integrin signaling in cancer. Semin Cancer Biol 2000 Dec;10(6):407-14
 
Integrin Signaling
 
Adhesive Signalling
 
Integrin and Laminin
 
Several integrin heterodimers act as laminin receptors on a variety of cell types
 
alpha 1 beta 1
 
alpha 2 beta 1
 
alpha 3 beta 1
 
alpha 6 beta 1
 
alpha 7 beta 1
 
alpha 6 beta 4
 
Microsc Res Tech 2000 Nov 1;51(3):280-301
 
Integrin and Laminin
 
Roles of laminin-binding integrins in adhesion-mediated events in vertebrates
 
embryonic development, cell migration and tumor cell invasiveness, cell proliferation, differentiation and basement membrane assembly
 
essential role for receptors in maintaining cell polarity and tissue architecture
 
Text from: Microsc Res Tech 2000 Nov 1;51(3):280-301
 
Basal Lamina Experiment 1
 
Basal Lamina Experiment 2
 
Neuromuscular junction
 
Basal lamina directs acetylcholinesterase (AChE) accumulation at synaptic sites in regenerating muscle
 
skeletal muscle damaged such that basal lamina sheaths of the muscle fibers spared
 
new myofibers develop within sheaths and neuromuscular junctions form at original synaptic sites
 
regenerated neuromuscular junctions have junctional folds and accumulations of acetylcholine receptors and AChE
 
Anglister L, McMahan UJJ Cell Biol 1985 Sep;101(3):735-43
 
Adhesion Junctions
 
Adherens (cell-cell)
 
cadherin (E-cadherin) Links to cadherin in neighboring cell
 
Adherens (cell-matrix)
 
Integrin Links to extracellular matrix
 
ECM Scaffold- Tissue Engineering
 
“Decellularized tissues and organs have been successfully used in a variety of tissue engineering/regenerative medicine applications, …Each of these treatments affect the biochemical composition, tissue ultrastructure, and mechanical behavior of the remaining extracellular matrix (ECM) scaffold, which in turn, affect the host response to the material.”
 
Decellularization of tissues and organs. Biomaterials. 2006 Jul;27(19):3675-83. Epub 2006 Mar 7.
 

Revision as of 21:05, 26 April 2009

ANAT3231 - Cell Biology
Lecture 12 and 13
School of Medical Sciences
The University of New South Wales Dr Mark Hill Cell Biology Laboratory Room G20 Wallace Wurth Building Email: m.hill@unsw.edu.au

UNSW Copyright Notice ExtraCellular Matrix (ECM) Cell-Cell, Cell-Matrix Adhesions

ECM References Essential Cell Biology Ch19 p594-604 Molecular Biology of the Cell p971-1009 Animal and Plant ECM Material secreted and deposited by cells

ANAT3231 Lecture 8 Extracellular matrix http://cellbiology.med.unsw.edu.au/units/science/lecture0812.htm ECM Function

Support for cells
Pattern of ECM regulates

Polarity cell division adhesion motility Development migration differentiation Growth factors ECM Structure- Glycoproteins Fibers Collagen- main fibers Elastin Hydrated Matrix Proteoglycans high carbohydrate Adhesive Glycoprotein Laminin Fibronectin Shapes and Sizes ECM molecules Collagen tensile strength and elasticity Tendons Cartilage Bone half total body proteins (by weight) Collagen Components Insoluble glycoprotein protein + carbohydrate Protein high glycine and 2 modified amino acids hydroxylysine hydroxyproline (gly-X-Y)n Carbohydrate glucose galactose Collagen Structure Collagen Protein 3 polypeptide (a) chains left hand helix, forms fibers 14 different (vertebrate) collagens by different combinations of a-chains numbered I - XIV Type I, II, III main fibers, flexible Type I bone, skin, tendons 90% of all collagen Type II cartilage Collagen Fibers Type I, II, III cross striated showing overlapping packing of individual collagen molecules Type IV fine unstriated sheet-like supportive meshwork mature basal laminae tracks for embryonic migration barriers for cell migration Type V-XII smaller diameter fibers than I-III no striations Collagen Fibers Collagen Non-striated Collagen Synthesis Endoplasmic Reticulum mRNA attached to ER protein synthesized into ER lumen 3 proto-a-chains form soluble procollagen moved to golgi apparatus Golgi Apparatus packed into secretion vesicles fuse with membrane Outside Cell procollagen processed by enzymes outside cell assemble into collagen fibers Collagen Biosynthesis Collagen Diseases - Excess excess collagen fibrosis lung- pulmonary fibrosis overproduction of collagen I liver- over consumption of alcohol arteries- atherosclerosis Collagen Diseases - Insufficient insufficient collagen Ehlers-Danlos syndrome rubber-man skin and tendons easily stretched contortionists often suffer from this disease Osteogenesis imperfecta brittle-bone syndrome mutation in Type I procollagen fail to assemble triple helix degrade imperfect collagen Leads to fragile bones Collagen Diseases scurvy dietary Vitamin C deficiency needed for hydroxylation Proline -> Hydroxyproline form too few hydrogen bonds in collagen skin, bone, teeth weakness and malformation blood vessels weakened, bleeding Glycosaminoglycans (Gags) 10% by weight but fill most of space unbranched polysaccharide chains disaccharide subunits amino sugar 4 groups hyaluronan chondroitin sulphate, dermatan sulphate heparan sulphate, heparin keratan sulphate Glycosaminoglycans- Hyaluronan Also called hyluronic acid or hyaluronate Development produce a “cell-free” space for cell proliferation and migration into heart, cornea Adult in areas of compression tissues, joints Hyaluronan Synthesis synthesized at plasma membranes nascent chains directly extruded into ECM Proteoglycans Proteoglycans- Function trap water resistant to compression return to original shape occupy space link to collagen fibers form network in bone combined with calcium hydroxyapatite, calcium carbonate Cell adhesion embryonic migration Proteoglycan- Disease Cancer development altered types and kinds of proteoglycans formed by cells normal cells -> malignant Arthritis Cartilage breakdown chondrocytes elicit a catabolic response which exceeds anabolism of new matrix molecules Degrade proteoglycan (aggrecan) Also a mouse model generates antibodies to proteogycan