Cell-to-Cell and Cell-to- Matrix Adhesions Test Your Knowledge: 1. Where would you find the basal lamina? Proteoglycans? Fibronectin? 2. Name one type of cell-to-cell connection. 3. Name one type of cell to extracellular matrix connection 4. Name one type of cell membrane to cytoskeleton connection. 5. Name one function of the extracellular matrix 6. True/False Specific extracellular matrix components can directly activate cytosolic signal transduction pathways.
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Cell-to-Cell and Cell-to-Matrix Adhesions Test Your Knowledge: 1.Where would you find the basal lamina? Proteoglycans? Fibronectin? 2.Name one type of.
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Cell-to-Cell and Cell-to-Matrix Adhesions
Test Your Knowledge:
1. Where would you find the basal lamina? Proteoglycans? Fibronectin?
2. Name one type of cell-to-cell connection.
3. Name one type of cell to extracellular matrix connection
4. Name one type of cell membrane to cytoskeleton connection.
5. Name one function of the extracellular matrix
6. True/False Specific extracellular matrix components can directly activate cytosolic signal transduction pathways.
Cells combine to form tissues. This requires that cells “adhere” to one another to form a functional unit.
Types of adhesion:
• Cell-to-cell adhesion
• Cell-to-extracellular matrix adhesion;
Types of interactions between adhesion proteins:
• Homophilic – adhesion created by interaction between two similar adhesion molecules
• Heterophilic – adhesion created by interaction between two different adhesion molecules or between adhesion molecules and cytoskeleton or extracellular matrix proteins
• Homotypic – adhesion between similar molecules
• Heterotypic – adhesion between different molecules
5 classes of CAMs
Not shown: mucins
Cell-to-cell adhesion molecules
1. Calcium dependent adhesion molecules (cadherins)• Evolutionarily ancient; widely expressed; over 12 different types known
• Almost all vertebrate cells express one or more
Structure: Single-pass transmembrane glycoprotein composed of about 700-750 residues
Type of binding:
Types:
•Interactive with actin cytoskeleton: Cadherins N; P; R; B; E
• A family of transmembrane adhesion molecules (usually glycoproteins) that exist in variable activation states
• Extracellular matrix receptors on integrins have selective affinity for certain matrix proteins; allows cells to explore their environment
Structure: have an alpha and a beta subunit (heterodimer); alternative splicing has led to 16 different chains and 8 different chains
Type of adhesion:
Function: WBC binding to endothelium;
Epithelial tissues – what do they need adhesion molecules for?tight junctionsadherens junctionsdesmosomehemidesmosome
Tight Junctions
Function:
Protein composition:
occludin
claudin
junction adhesion molecules (JAMs)
Cytosolic face
Adherens junctions (adhesion belt); attach to actin
Desmosomes; attach to intermediate filaments
Focal adhesions
Hemidesmosomes
Adherens Junctions
Composition: cadherens
Function: can contract (with help of myosin)
Folding of sheets into tubes during morphogenesis, other folding processes during morphogenesis
Binding partners:
catenins, and via catenins to cytoskeleton (actin)
desmosomepemphigus
Focal Adhesions
Examples: myotendinous junction
fibroblast migration in connective tissue
Basal Lamina – extracellular matrix; a sheetlike meshwork underlying or surrounding groups of cells
Function :
Components of the basal lamina; produced by cells that rest on it (mainly fibroblasts); sometimes called the basement membrane
• Type IV collagen
• Laminins
• Entactin (nidogen and laminin)
• Perlecan
The regulatory factors which impact on matrix synthesis, degradation and function are many and include 'growth factors', cytokines, hormones, vitamins, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
Vitamins: C, D
Hormones: estrogens, glucocorticoids,
Matrix Metalloproteinases MMP: zinc containing enzymes that degrade most molecules of the ECM
Tissue Inhibitors of Metalloproteinases TIMP: zinc binding endopeptidases
Growth Factors: TGFß promotes cellular movement through matrix, and is involved in imflammation and repair
Proteoglycans – glycoproteins containing covalently linked polysaccharide chains called glycosaminoglycans (GAGs); high viscosity and low compressibility
hyaluronanAlso: chondroitin or dermatan sulfate, keratan sulfate, heparan sulfate/heparin-
Common structural make-up of GAGs attachment to proteins; proteoglycans or mucopolysaccharides
95% carbohydrate by weight
Possible functions:
• Selective sieve; regulate movement of molecules and cells
• Chemical signaling between cells; bind certain growth factors (FGF) to stimulate proliferation in the area; TGF binds to several core proteins of the proteoglycan group
• Bind and regulate proteases and protease inhibitors (may restrict range of action, sterically block activity, provide a reservoir for later release, prolong action, or alter concentration)
GAG Localization Comments
Hyaluronatesynovial fluid, vitreous humor,
ECM of loose connective tissue
large polymers, shock absorbing
Chondroitin sulfate
cartilage, bone, heart valves most abundant GAG
Heparan sulfate
basement membranes,components of cell surfaces
contains higher acetylated
glucosamine than heparin
Heparin
component of intracellular granules of mast cells
lining the arteries of the lungs, liver and skin
more sulfated than heparan sulfates
Dermatan sulfate
skin, blood vessels, heart valves
Keratan sulfate
cornea, bone, cartilage aggregated with
chondroitin sulfates
ECM proteins in connective tissue
• Collagen
• Proteoglycans
• Adhesion proteins
• Hyaluronan
• Elastic fibers
Tendon – dense connective tissue
Type IV collagen
• Repeating sequence (Glycine – X –Y)n X = proline Y= hydroxyproline
• Left handed helix. N-terminal and C-terminal ends have globular domains (solubility; cleaved when secreted from cell - insoluble)
• In ER and Golgi they are glycosylated, OH groups added, S-S links three chains
• End result a triple helix
Different types of collagen can co-assemble to form large fibers. Type VI +type I in tendons, form in direction of stress. Type II and Type IX oriented randomly and are in cartilage for strength and compressibility.
Function: organization of basement membrane; have binding sites for itegrin receptors (important in embryonic development and tissue remodeling)
•Laminins are tightly associated with entactin or nidogen a 150-kD sulfated glycoprotein, which also binds to type IV collagen. As a result of these multiple interactions, laminin, entactin, type IV collagen, and perlacan form crosslinked networks in the basal lamina.
Cartilage proteoglycan aggregate
Adhesions between non-epithelial, cells and the extracellular matrix – short and long term adhesions that help in motility
• Focal adhesions
• Focal contacts
• Focal complexes,
• 3D adhesions
• Fibrillar adhesions
• Podosomes
Two conformations of integrins
Change in conformation transferred to other proteins scaffolded to internal signaling pathways