Topic 12: Extracellular Matrix and Cell-Cell Interactions Flashcards
Extracellular Matrix (ECM)
- where most animal cells in tissues are embedded
- fills space between cells and binds cells and tissues together
- amount of ECM varies within tissue type
Epithelial Tissues
- basal lamina underlies epithelial cells, and binds them to underlying connective tissues
Muscle, Adipose, Nerve Tissues
- surrounded by a thin basal lamina
Connective Tissue
- bone, tendon, cartilage, loose connective tissue underlying skin
- composed predominantly of ECM
- -> component principally responsible for form and function of tissue
- cells play a generative and supportive role for the ECM in these tissue types
Basal Lamina
- sheetlike ECM
Organization of ECM
- composed of tough fibrous structural proteins embedded in a gel-like polysaccharide material (GROUND SUBSTANCE)
- -> diff. tissues vary in amount and organization of above components
Specialized Adhesion Proteins
- anchor cells to ECM
Collagen
- the major structural protein of the ECM
- single most abundant protein in animal tissues
- large family of proteins containing at least 27 diff. members
- -> form straight fibrils and fibres and networks
Collagen Classes
- Fibril-forming (type I)
- Network-forming (type IV)
- Fibril-associated
- Anchoring
- Transmembrane
Basic Structure of Collagen
- amino acid primary sequence = triple repeat of Gly-X-Y
- X: proline; Y: hydroxyproline
- -> stabilizes collage triple helicies
- hydroxylysine also present
- 3 polypeptide chains wound around each other**
Collagen Fibrils
- formed when collagen triple helices line up in staggered arrangement and are cross-linked together
- assembly takes place in ECM following secretion of procollagen from cell via ER/Golgi pathway
Procollagen
- partially processed precursor of collagen
Collagen Fibres
- bundles of collagen fibrils
- collagen is secreted as subunits of procollagen that then is assemble into fibril and fibres outside of cell
Elastic Fibres
- found in connective tissues
- are particularly abundant in organs that regularly stretch and then return to their original shape
- ex) lungs
Elastin
- principal protein of elastic fibres
- cross-linked into a network by covalent bonds formed between the side chains of lysine residues
Glycosaminoglycans (GAGs)
- gel-forming (frequently sulphated) polysaccharides of ECM that consist of repeating units of disaccharides
- neg. charge binds pos. charged ions, attracting and trapping water molecules, creating hydrated gel-like structure
- GAGs covalently linked to specific proteins to form hight order structures known as proteoglycans
Proteoglycans
- large, branching glycoproteins containing up to 95% carbohydrate by weight
- ex) aggrecan (chondroitin sulfate is the GAG attached to a core protein
Higher Order Organization of Matrix Polysaccharides
i) GAGs
ii) Proteoglycans
iii) Larger proteoglycan aggregates
Larger Proteoglycan
Aggregates
- A number of proteoglycans interact with hyaluronan chains (GAGS) to form large complexes in the extracellular matrix
Matrix Adhesion Proteins
- the final class of ECM constituents
- responsible for linking the components of the matrix to one another and the the surfaces of cells
- Fibronectin and Laminin
Fibronectin
- dimeric glycoprotein
- the principal adhesion protein of connective tissues
- consists of proteoglycan, integral, collagen binding sites
Laminin
- the principal adhesion protein of the basal lamina
- a heterotrimer with 3 subunits
- consists of Nidogen and Agrin
Nidogen
- protein that links laminin to collagen type IV
Agrin
- large proteoglycan of ECM
Integrins
- major cell surface proteins responsible for the attachment of cells to the ECM
- can bind to peptide sequences in collagen, fibronectin, laminin
- serve as anchors for the cytoskeleton within the cell
- provides linkage between cytoskeleton intracellularly and ECM
- serve as receptors that activates intracellular signalling pathways in response to signals within ECM
- -> control cell movement, proliferation
Structure of Integrins
- consist of dimers of 1 alpha and 1 beta subunit
- outer receptor (matrix binding) and inner (cytoskeleton binding) regions
Types of Cell-Matrix Interactions
- Focal Adhesions
- Hemidesmosomes
- both form localized sites of adhesion between the cell and ECM
Focal Adhesions
- a type of cell-matrix junction
- attaches a variety of cells, including fibroblasts to ECM
- link to actin filaments of cytoskeleton
- this type of integrin binding is is reversible
- -> very important for movement over surfaces
- can be stable or turn over very rapidly (ex. migrating cells)
Hemidesmosomes
- type of cell-matrix junction
- mediate epithelial cell attachments at which a specific integrin interacts with laminin in the basal lamina
- link to intermediate filaments of cytoskeleton
- strongest cell-matrix junction
- very stable and long-term junctions
3 Categories of Cell-Cell Junctions
- Stable Adhesion Junction
- adherens and desmosome - Tight Junctions
- Gap Junctions
Adheren Junctions
- involves a family of integral plasma membrane proteins in adjacent cells (cadherins)
Cadherins
- link the actin cytoskeleton of adjacent cells via adheren junctions
Desmosomes
- involve a family of cadherins known as desmoglein and desmocollin
Desmoglein and Desmocolling
- link the cytoskeletons of adjacent cells via desmosome junctions
Tight Junctions
- critically important to the function of epithelial cell sheets (ex. intestinal)
- form a barrier between fluid compartments
- -> molecules move across the cell so cell can regulate it
- separate apical and basal domains of p. membrane
- -> prevent lateral movement of integral membrane proteins between domains of cell
- have minimal adhesive strength
Junctional Complexes
- a region of cell-cell contact containing a tight junction, adherens junction and a desmosome
Gap Junctions
- important for cell-cell (intracellular) communication and coordination of cellular activity
- open channels through the p. membrane that provide direct connections btwn cytoplasm of adj. cells
- allow for open flow of ions and other small molecules
- provide mechanism to couple metabolic and electrical activity of adj. cells
Connexin
- member of a family of transmembrane proteins that form gap junctions
Connexon
- a cylinder formed by 6 connexions in the plasma membrane