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Adhesion Cell junctions. Dr. habil. Kőhidai László Assoc. Professor Dept. Genetics, Cell- and Immunobiology Semelweis University. 20 16 – ED. Significance of cell-adhesion: formation of cell la yers. Significance of cell-adh es ion: Formation of multiple layers of cells.
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Adhesion Cell junctions Dr. habil. Kőhidai László Assoc. Professor Dept. Genetics, Cell- and Immunobiology Semelweis University 2016– ED
Significance of cell-adhesion: Formation of multiple layers of cells
Lymphocytes cross the endothel „Rolling” Entry Adhesion Migration homing receptor vascular addressin
Main adhesion molecules expressed on the cells during adhesion • Cadhedrins homophil • Selectins heterophil • Integrins heterophil • Adh. mol. with immunoglobulin homophil domain { Ca2+
i.e. cadherin cyto- skele- ton i.c. linker prot. i.e. integrin ECM
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
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
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 (?!)
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
Junctional complexes • Tight junction • Zonula adherens • Desmosome • Gap junction • Hemidesmosome • Interdigitation
Intercellular space 0.6 mm Transmembrane proteins occludin Lipid bilayer Cytoplasmic face Tight junction = zonula occludens
Negative staining to detect „insulating” effect of tight junction
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
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
Desmosome = macula adherens Cell to cell, snap-like junction
cytoplasmatic plaque desmoplaquin, plactoglobin Desmosome actin intermedier filaments desmosomal cadherins i.e. desmoglein, desmocollin
TEM structure of desmosome Cytoplasmatic plaque Intermedier filaments (i.e. keratin) cadherins
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
Role of gap junction • Transportofneurotransmitters, cAMP, • Ca 2+ • Signaling in early embryo
Plasmodesmata sER cytoplasm desmotubule cellwall membrane plasmodesmata Gap junction-like function Viral infection results in the increase of pore diameter
Plasmodesmata ER membrane desmotubule
Hemidesmosome Fixing of epithelial cells to the basal membrane
Interdigitation Characteristic between epithelial cells
Structure of focal contact actin filament a actinin vinculin paxillin talin integrin fibronectin
Focal contacts actin vinculin
Extracellular matrix - Function • Influence on migration of the cells • Regulation of activity of molecules released • Co-receptors
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
Fibronectins collagen cell RGD Dimer composed by different channels – alternative splicing heparin
Fibronectins Gly Arg Asp • Glycoproteins • Dimer-structure • RGD (Arg-Gly-Asp) • Plasma fibronectins • Gene „K.O.” experiments
Basal lamina Cell Connective tissue Layers: lamina lucida lamina densa lamina fibroreticularis Components: IV. collagen laminin perlecan entactin
SEM image of basal lamina epithelial cells basal membrane collagen fibrils
Collagen IV Entactin Perlecan Laminin
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
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
Negative staining of collagen fibrils gaps between collagen molecules collagen
B2 chain B1 chain A chain a-helix Globular domains Laminin • each chain has more types • 18 isoforms of laminin • diversities in tissues
strech relax Elastin fibre of elastin cross-links