Week 10: ECM and Cell Interactions

Question 1

What are the two main tissue types in animals?

Answer 1

epithelial (sheets of polarized cells with discrete functional domains at opposite ends - apical and basal) and connective tissue (more loosely organized - cells attached to each other, a ECM or both)

Question 2

Describe the regions of epithelial tissue

Answer 2

Apical region, basolateral region, basal lamina, basement membrane and ECM.

Question 3

How are tissues held together?

Answer 3

held together by cell-cell adhesions and/or ECM

Question 4

What are the 3 types of ECM in animals?

Answer 4

bone - (rigid ECM w/small number of interspersed cells)

cartilage (mostly matrix materials more flexible than bones)

connective tissue (surrounding glands and blood vessels - relatively gelatinous and contains interspersed fibroblast cells)

Question 5

What are fibroblasts?

Answer 5

produce the ECM of connective tissues

Question 6

Describe collagen structure

Answer 6

Single collagen polypeptide chain becomes a triple-stranded collagen molecule which joins with many to form a collagen fibril which join together to form a collagen fiber .

Question 7

What is collagens purpose?

Answer 7

ensile strength of ECM - flexibility

Question 8

How is collagen formed?What is the purpose of this path?

Answer 8

Procollagen precursors are found in secretory vesicle which is then secreted and then terminal procollagen extensions are cleaved by proteinase to form mature collagen outside the cell which self-assembles into fibrils. Unstructured peptides at either end of procollagen prevent collagen fibrils from assembling inside the fibroblast secretory vesicle.

Question 9

How do collagen fibrils arrange in skin and what does incorrect assembly cause?

Answer 9

Collagen fibrils in skin - arranged in plywood like pattern. Incorrect collagen assembly - hyperextensible skin (ie. EDS).

Question 10

What fills the spaces between collagen fibrils in skin? What does role does collagen play? GAGs?

Answer 10

Gels of polysaccs and proteins fill spaces and resists compression. Collagen provides tensile strength to resist stretching. Compression capabilities in ECM provided by GAGs - negatively-charged repeating disacchs.

Question 11

What is the structure of a GAG?

Answer 11

Repeating disaccharide of N-acteylglucosamine and glucuronic acid

Question 12

What do proteoglycans and GAGs do? What happens when the amount of GAGs is low? High?

Answer 12

Proteoglycans and GAGs can form large aggregates. In dense compact connective tissue (ie. tendon) - amount of GAGs low - ECM mostly collagen. In loose connective tissue - amount of GAGs high - collagen low.

Question 13

Describe the structure of an aggrecan aggregate

Answer 13

Hyaluronan molecule is studded with link proteins that support core protein branchings which have further branchings of chondroitin sulfate and keratan sulfate.

Question 14

Describe integrins

Answer 14

Integrins couple ECM to cytoskeleton - two chains (alpha and beta) - cytoplasmic domain with binding sites for actin binding proteins ie. talin (link to actin cytoskeleton) - extracellular domain - other binding sites for proteins (ie. fibronectin - ECM protein - allows cell to bind ECM).

Question 15

What is fibronectin?

Answer 15

Fibronectin- link b/w cell and ECM - binding sites for integrin and collagen fibrils. They have collagen binding sites and cell attachment sites. It binds the collagen fibril to the integrin dimer (bound to adaptor proteins which bind to actin filaments).

Question 16

How to integrins switch to active conformation?

Answer 16

Integrins switch to active conformation when it binds to molecules on either side of plasma membrane.

Question 17

How does focal adhesion occur with fibroblast in ECM?

Answer 17

Integrins bind to matrix and also to talin which is bound to vinculin which is bound to actin filaments that are attached to one another via alpha actinin.

Question 18

What are 5 kinds of cellular connections

Answer 18

Simple, stratified, columnar, cuboidal and squamous.

Question 19

Describe epithelial cells

Answer 19

Epithelial sheets are polarized - rest on basal lamina - specialized sheet of ECM. ie. functionally polarized cells in interstine.

Question 20

Describe tight junctions

Answer 20

Tight junctions make epithelium leak-proof and separate apical and basal surfaces

Question 21

What are the 3 main types of cytoskeleton-linked cell junctions?

Answer 21

Three main types of cytoskeleton-linked cell junctions (bind epithelial cells to one another and basal lamina):

1. Adherens junctions (bind one epithelial cell to another)
2. Desmosomes (bind one epithelial cell to another)
3. Hemi-desmosomes (bind epithelial cells to basal lamina)

Question 22

Describe adherens junctions

Answer 22

• cadherin molecules in adjacent cells are identical. Cadherins have intracellular and extracellular domains. Cadherins interacting with actin filaments.

Question 23

Describe adherens junctions in SI

Answer 23

Adherens junctions form adhesion belts around epithelial cells in SI

Question 24

Describe tissue-specific types of cadherins

Answer 24

Are tissue-specific types of cadherins - E-cadherins are found on epithelial cells - P-cadherins in placenta. Amount and type of cadherins on cell surfaces help segregate cells into specific tissues - important in embryonic development.

Question 25

What occurs with cell adhesion in cancer

Answer 25

Loss of cell adhesion also occurs in cancer cells as they acquire ability to metastasize

Question 26

Describe bending of epithelial sheets

Answer 26

Epithelial sheets can bend to form tube or vesicle

Question 27

Describe desmosomes

Answer 27

link keratin intermediate filaments of one epithelial cell to those of another with cadherin proteins (different from those in adherens junctions)

Question 28

Describe hemidesmosomes

Answer 28

anchor keratin filaments in epithelial cell to basal lamina

Question 29

Describe gap junctions

Answer 29

allow inorganic ions and small water-soluble molecules (~1000 daltons) to move from the cytosol of one cell to other. Flow creates electrical and metabolic coupling between cells. Gap junctions in cardiac muscle cells provide electrical coupling that allows electrical waves of excitation to spread throughout cells - coordination.

They respond to extracellular or intracellular signals ie. dopamine reduces gap junction communication between certain neurons in retina of animals when secreted in response to increased light.

6 subunits of connexin form a connexon.