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Adhesion Cell junctions

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Title: Nincs diac m Author - Last modified by: K hidai L szl Created Date: 2/12/2000 5:34:42 PM Document presentation format: Diavet t s a k perny re – PowerPoint PPT presentation

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Title: Adhesion Cell junctions


1
Adhesion Cell junctions
Dr. habil. Kohidai László Assoc. Professor Dept.
Genetics, Cell- and Immunobiology Semelweis
University
2008
2
Significance of cell-adhesion formation of cell
layers
3
Significance of cell-adhesion Formation of
multiple layers of cells
4
Lymphocytes cross the endothel
Rolling
Entry
Adhesion
Migration
homing receptor
vascular addressin
5
Main groups of cell adhesion molecules
6
Main adhesion molecules expressed on the cells
during adhesion
  • Cadhedrins homophil
  • Selectins heterophil
  • Integrins heterophil
  • Adh. mol. with immunoglobulin homophil domai
    n


Ca2
7
i.e. cadherin
cyto- skele- ton
i.c. linker prot.
i.e. integrin
ECM
8
Cadherin
Ca2
Ca2
  • Homophil connection
  • Cell-cell
  • Ca2-dependent binding
  • I.c. anchored to actin or
  • intermedier filamentum
  • Significant role in
  • development
  • of vertebrates

Ca2
catenin
  • Tissue-specificity
  • N - nerve
  • P - placenta
  • E - epithelial

actin or IF
9
CAM Cell Adhesion Molecules
  • 5 pcs. Ig-type domain
  • Ca 2 indep. adhesion
  • Homophi connection - typical
  • Heterophil connection - rare
  • More than 20 variations
  • Expressed in the critical phase of
  • development

Ig-like domains
  • Tissue-specificity
  • N-CAM - neuron
  • L-CAM - liver

In melanoma relation between ICAM-1 density
and the Metastatic activity of the tumour
10
Selectins
Lectin type proteins, Carbohydrate specificity
Tissue-specificity E - epithelial L -
lymphoid P - placenta
L selectin it has role in the initial phase of
adhesion in newborns the level of L sel. is
low the low number of inflammations (?!)
11
Integrin
b
  • Ca2-dependent binding
  • Heterophil connection
  • Focal contacts
  • Its i.c. linker proteins are
  • i.e.. talin, a-actinin, vinculin
  • RGD sequ. Is significant in
  • e.c. binding
  • Partner molecules
  • fibronectin
  • laminin
  • collagen

a
S
S
Deficiency (b) the adhesion of leukocytes
affected, results the increase of inflammations
12
Cell-cell junctions
13
Junctional complexes
  • Tight junction
  • Zonula adherens
  • Desmosome
  • Gap junction
  • Hemidesmosome
  • Interdigitation

14
Tight junction zonula occludens
15
Negative staining to detect insulating effect
of tight junction
16
Transport accross tight junction
17
System of occludin lines
18
Role of tight junction
  • Mechanical connection
  • Barrier
  • Inhibits
  • entry of water-soluble molecules
  • lateral diffusion of membrane-components
  • Ca2 is required for the connections of
    occludins
  • Permeability inorganic small substances
  • amino acids
  • monosaccharides

19
Septate junction
  • on the apical part of the cells
  • they form a continous belt (like z. adherens)
  • promote to stick together the cells
  • actin is anchored in this junction

20
Desmosome macula adherens
Cell to cell, snap-like junction
21
cytoplasmatic plaque desmoplaquin, plactoglobin
Desmosome
actin
intermedier filaments
desmosomal cadherins i.e. desmoglein, desmocollin
22
Components of desmosomes
23
TEM structure of desmosome
Cytoplasmatic plaque
Intermedier filaments (i.e. keratin)
cadherins
24
Submembraneous network connecting desmosomes
25
Gap junction (1958, 1968)
  • Bridges the 2-4 nm gap between the neighbour
    cells
  • Hexagonal channel is formed (connexon)
  • The wall of the channel is composed by 6
    connexins
  • (4 helical components)
  • The distribution of channels is tissue- or
    cell-specific
  • due to the difference of connexins
  • Accross channels substances are transmitted
  • (max MW. 1000) by a regulated mechanism

26
Gap junction
27
Gap junction
28
Role of gap junction
  • Transport of neurotransmitters, cAMP,
  • Ca 2
  • Signaling in early embryo

29
Plasmodesmata
sER
cytoplasm
desmotubule
cellwall
membrane
plasmodesmata
Gap junction-like function Viral infection
results in the increase of pore diameter
30
Plasmodesmata
ER
membrane
desmotubule
31
Hemidesmosome
Fixing of epithelial cells to the basal membrane
32
Basal striation
33
Interdigitation
Characteristic between epithelial cells
34
Structure of focal contact
actin filament
a actinin
vinculin
paxillin
talin
integrin
fibronectin
35
Focal contacts
actin
vinculin
36
Extracellular Matrix
37
Extracellular matrix - Function
  • Influence on migration of the cells
  • Regulation of activity of molecules released
  • Co-receptors

38
Extracellular matrix Building blocks
  • Glycosaminoglycans (GAG-s)
  • heparan sulfate - basal membr., cell surface
  • keratan sulfate - cornea, bone
  • chondroitin sulfate cartilage, bone, heart
  • hyaluronate - synovial fluid
  • dermatan sulfate - blood vessels, heart
  • Core-proteins aggrecan decorin
  • collagen elastin - structure
  • fibronectin laminin - adhesion

39
Fibronectins
collagen
cell
RGD
Dimer composed by different channels
alternative splicing
heparin
40
Fibronectins
Gly
Arg
  • Glycoproteins
  • Dimer-structure
  • RGD (Arg-Gly-Asp)
  • Plasma fibronectins
  • Gene K.O. experiments

Asp
41
Basal lamina
Cell Connective tissue
Layers lamina lucida lamina densa lamina
fibroreticularis
Components IV. collagen laminin perlecan
entactin
42
SEM image of basal lamina
epithelial cells
basal membrane
collagen fibrils
43
Main proteins composing the basal lamina
44
Collagen IV
Entactin
Perlecan
Laminin
45
Collagen
  • Fibrils (diam.10-300 nm)
  • More than 15 types
  • I., II., III., V., XI. formation of fibrils
  • IV., VII. network
  • IX., XII. association of fibrils

46
Synthesis and association of collagen filament
synthesis of a-chain
Pro, Lys hydroxilation
glycosylation
assembly
organization into a fiber
formation of triple helix
secretion
splitting of procollagen
building into fibrill
47
Negative staining of collagen fibrils
gaps between collagen molecules
collagen
48
SEM image of collagen fibrils
49
Laminin
  • each chain has more types
  • 18 isoforms of laminin
  • diversities in tissues

50
Elastin
fibre of elastin
cross-links
51
Aggrecan
  • One complex of aggrecan
  • M.W. about 108
  • Volume 2x10-12 ml
  • ( bacterium)

52
Complex of aggrecan
1 mm
Core prot.
Hyaluronan
Linker proteins
Keratin sulfate
Chondroitin sulfate
53
Matrix types produced by vertebrate cells
Abbr. ChS chondroitin sulfate DS dermatan
sulfate HS heparan sulfate Hep -
heparin
54
Clinical approaches
hydroxy-Pro ? hydroxy-Lys ? cross-linking
? N-term. propeptide
- poor wound healing - hyperextensibility -
musculo-skeletal deformities
Collagen
55
Complexity of cell adhesion
56
Interactions in focal contact
Fimbrin Nexilin Tensin A-Actinin Talin Paxillin
Caveolin Zyxin Palladin Vinexin Ponsin Integrin
, Syndecan-4, Leukocyte common antigen
57
Protein associated to actin filaments
Zonula adherens E cadherin Catetin
Vinculin a-actinin Plactoglobin Adhesion
plaque Integrin a -actinin Vinculin Talin
58
Induction of integrins
Binding site in matrix
e.c. matrix
active integrin
Binding site in cytoskeleton
P
P
P
P
actin
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