Topic 12: Extracellular Matrix and Cell-Cell Interactions

Question 1

Extracellular Matrix (ECM)

Answer 1

• 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

Question 2

Epithelial Tissues

Answer 2

• basal lamina underlies epithelial cells, and binds them to underlying connective tissues

Question 3

Muscle, Adipose, Nerve Tissues

Answer 3

• surrounded by a thin basal lamina

Question 4

Connective Tissue

Answer 4

• 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

Question 5

Basal Lamina

Answer 5

• sheetlike ECM

Question 6

Organization of ECM

Answer 6

• 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

Question 7

Specialized Adhesion Proteins

Answer 7

• anchor cells to ECM

Question 8

Collagen

Answer 8

• 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

Question 9

Collagen Classes

Answer 9

1. Fibril-forming (type I)
2. Network-forming (type IV)
3. Fibril-associated
4. Anchoring
5. Transmembrane

Question 10

Basic Structure of Collagen

Answer 10

• 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**

Question 11

Collagen Fibrils

Answer 11

• 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

Question 12

Procollagen

Answer 12

• partially processed precursor of collagen

Question 13

Collagen Fibres

Answer 13

• bundles of collagen fibrils

- collagen is secreted as subunits of procollagen that then is assemble into fibril and fibres outside of cell

Question 14

Elastic Fibres

Answer 14

• found in connective tissues
• are particularly abundant in organs that regularly stretch and then return to their original shape
• ex) lungs

Question 15

Elastin

Answer 15

• principal protein of elastic fibres

- cross-linked into a network by covalent bonds formed between the side chains of lysine residues

Question 16

Glycosaminoglycans (GAGs)

Answer 16

• 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

Question 17

Proteoglycans

Answer 17

• large, branching glycoproteins containing up to 95% carbohydrate by weight
• ex) aggrecan (chondroitin sulfate is the GAG attached to a core protein

Question 18

Higher Order Organization of Matrix Polysaccharides

Answer 18

i) GAGs
ii) Proteoglycans
iii) Larger proteoglycan aggregates

Question 19

Larger Proteoglycan

Aggregates

Answer 19

• A number of proteoglycans interact with hyaluronan chains (GAGS) to form large complexes in the extracellular matrix

Question 20

Matrix Adhesion Proteins

Answer 20

• 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

Question 21

Fibronectin

Answer 21

• dimeric glycoprotein
• the principal adhesion protein of connective tissues
• consists of proteoglycan, integral, collagen binding sites

Question 22

Laminin

Answer 22

• the principal adhesion protein of the basal lamina
• a heterotrimer with 3 subunits
• consists of Nidogen and Agrin

Question 23

Nidogen

Answer 23

• protein that links laminin to collagen type IV

Question 24

Agrin

Answer 24

• large proteoglycan of ECM

Question 25

Integrins

Answer 25

- 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

Question 26

Structure of Integrins

Answer 26

- consist of dimers of 1 alpha and 1 beta subunit | - outer receptor (matrix binding) and inner (cytoskeleton binding) regions

Question 27

Types of Cell-Matrix Interactions

Answer 27

1. Focal Adhesions 2. Hemidesmosomes - both form localized sites of adhesion between the cell and ECM

Question 28

Focal Adhesions

Answer 28

- 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)

Question 29

Hemidesmosomes

Answer 29

- 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

Question 30

3 Categories of Cell-Cell Junctions

Answer 30

1. Stable Adhesion Junction - adherens and desmosome 2. Tight Junctions 3. Gap Junctions

Question 31

Adheren Junctions

Answer 31

- involves a family of integral plasma membrane proteins in adjacent cells (cadherins)

Question 32

Cadherins

Answer 32

- link the actin cytoskeleton of adjacent cells via adheren junctions

Question 33

Desmosomes

Answer 33

- involve a family of cadherins known as desmoglein and desmocollin

Question 34

Desmoglein and Desmocolling

Answer 34

- link the cytoskeletons of adjacent cells via desmosome junctions

Question 35

Tight Junctions

Answer 35

- 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

Question 36

Junctional Complexes

Answer 36

- a region of cell-cell contact containing a tight junction, adherens junction and a desmosome

Question 37

Gap Junctions

Answer 37

- 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

Question 38

Connexin

Answer 38

- member of a family of transmembrane proteins that form gap junctions

Question 39

Connexon

Answer 39

- a cylinder formed by 6 connexions in the plasma membrane