AC Lecture 38-39: Intercellular architecture

Question 1

List the different types of cell adhesion molecules (CAMs).

Answer 1

cadherins
the Ig superfamily
integrins
selectins

Question 2

How are CAMs used?

Answer 2

regulate cell migration, proliferation, and cell death

Question 3

What are CAMs?

Answer 3

molecules that maintain adhesion between cells and other cells as well as between cells and their extra cellular matrix

Question 4

What are the characteristics of cadherins?

Answer 4

homophelic
Ca2+ binding
bind actins and IF

Question 5

What are the characteristics of integrins?

Answer 5

connect cells to extracellular matrix (heterophilic binding)
bind actins (except for alpha6beta4 interacts with IFs at hemidesmosomes)
cell matrix receptors that require Ca2+ or Mg2+ for ligand binding

Question 6

What are the characteristics of selectins?

Answer 6

mediate Ca2+ dependent cell:cell adhesion in the bloodstream
mostly on immune cells
help cells find their way out of the blood stream

Question 7

What are the functions of the ECM?

Answer 7

hold tissues together
provide cushioning (cartilage) and strength (tendons)
act as a reservoir for growth factors

Question 8

Why do epithelial cells have a polarized cell organization?

Answer 8

divide different body cavities
provide barriers between the gut and the blood and the blood brain barrier
different functions (absorption of nutrients on one membrane and their secretion from another)

Question 9

List the kinds of epithelial cells.

Answer 9

simple columnar (mucus secreting)
simple squamous (found lining blood vessels)
transitional (found in cavities subject to expansion such as bladder)
stratified squamous (found in mouth and vagina linings acts to resist abrasion)

Question 10

How do we describe the orientation of membranes?

Answer 10

apical (outer facing; typically have large surface area and villi)
lateral and basal (separated from the apical via specialized cell junctions)

Question 11

What is “inside-out” signaling?

Answer 11

where intracellular events promote interactions between the cell and the ECM

Question 12

What is “outside-in” signaling?

Answer 12

extracellular events (such as ligand binding) that cause interactions between the cell and the ECM

Question 13

List the kinds of cell junctions in epithelial cells.

Answer 13

Tight junctions
anchoring junctions (adherens junctions
desmosomes)

Question 14

What are tight junctions?

Answer 14

(occluding junctions)
seal epithelial cells together in sheets
prevents passage of small molecules between cells (allow for separation of body cavities)
separate the apical and basolateral surfaces

Question 15

What are anchoring junctions?

Answer 15

join cells to each other and to ECM

can be adherens junctions or desmosomes

Question 16

What are adherens junctions and desmosomes?

Answer 16

hold cells together and are formed by focal adhesions and hemidesmosomes (bind cells to ECM)

Question 17

How do the two kinds of junctions differ?

Answer 17

types of protein that perform the anchoring functions and the cytoskeletal filament types that attach on the inside of the cell
focal adhesions: integrin proteins bind to ECM and attach to actin inside the cell
hemidesmosomes: intermediate filaments bind inside the cell

Question 18

What are cadherins?

Answer 18

large glycoproteins that link by a homophilic mechanism

linc to actin cytoskeleton via catenins (adapter proteins)

Question 19

What mediates integrin’s interaction with actin?

Answer 19

anchor proteins (e.g. talin, alpha-actin, and filamin)

Question 20

What proteins are found in tight junctions?

Answer 20

claudins

occludins

Question 21

What are communicating (gap) junctions?

Answer 21

clusters of pores found in virtually every cell in the body composed of connexins
used for amplification of a response across a tissue from a local source (e.g. neuromuscular junction)

Question 22

List diseases caused by mutation in connexin genes.

Answer 22

sensorineural hearing loss (GBJ2 gene)
demyelinating disease (CMT)
skin diseases and arythmias
congenital cataracts

Question 23

What is the ECM?

Answer 23

a mixture of proteins and polysaccharides

abundant in bone and cartilage (low amounts in brain and spinal cord)

Question 24

How is the ECM produced?

Answer 24

by cells such as fibroblasts in the local matrix (can be specialized for different kinds of ECM such as osteoblasts that make bone)

Question 25

What are the main components of the ECM?

Answer 25

collagens proteoglycans multi-adhesive connectors (e.g. fibronectin and laminin)

Question 26

What is the basal lamina?

Answer 26

flexible mats of specialized matrix that underlies epithelial cell sheets and tubes separates cells from surrounding connective tissue and serves as a highly selective filter

Question 27

What are the components of the basal lamina?

Answer 27

laminins Type IV collagen Perlecan Nidogen

Question 28

What are laminins?

Answer 28

large cross shaped proteins containing three chains bind each other via N-terminal globular domains to form mesh-like network help cells interact with ECM main ligand for integrins in hemidesmosomes

Question 29

What is Type IV collagen?

Answer 29

forms a 2D lattice on the underside of the basil lamina towards the connective tissue triple helical structure with N and C terminus

Question 30

What is perlecan?

Answer 30

form of proteoglycan contains a core polypeptide attached to large number of carbohydrate chains of glycosaminoglycans (GAGs) integrates nidogen

Question 31

What is nidogen?

Answer 31

protein that crosslinks all other compounds together including the other components of the basil lamina

Question 32

How does connective tissue differ from solid tissues?

Answer 32

connective tissue (e.g. tendons and cartilage) are mostly ECM rather than cells

Question 33

What is the composition/arrangement of tendons?

Answer 33

``` Collagen I (packed together in microfibrils) are packed into fibrils which are packed into collagen fibers these collagen fibers are then offset/staggered to give the striated appearance and are crosslinked to stabilize the side by side packing ```

Question 34

What can be caused by mutation in Type I collagen?

Answer 34

osteogenesis imperfecta

Question 35

What is the composition/arrangement of cartilage?

Answer 35

Type II collagen in a mesh framework

Question 36

What are proteoglycans?

Answer 36

formations of carbohydrates and proteins that form the basis of higher order ECM structures GAG chains bind water and provide hydration to resist compressive forces

Question 37

Where are proteoglycans found?

Answer 37

abundant in cartilage and neural ECM

Question 38

What is fibronectin?

Answer 38

a large, multi-domain glycoprotein that assembles outside of cells into fibrillar structures and interacts with integrins as well as other extracellular matrix proteins (e.g. collagen, fibrin, and heparan sulfate proteoglycans)

Question 39

What is elastin?

Answer 39

fibers that allow for recoil after transient stretch sheathed by microfibrils containing fibrillin rich in glycine, proline, and hydroxyproline

Question 40

What happens when there are mutations in fibrillin?

Answer 40

Marfan syndrome (leads to defects in tissues rich in elastin fibers such as the aorta which is prone to rupture in extreme cases)

Question 41

Describe DMD.

Answer 41

Duchenne Muscular Dystrophy is caused by mutations to dystrophin (DMD gene) part of a complex that connects the ECM to actin inside muscle cells (dystrophin glycoprotein complex) to help stabilize the muscle cells and integrate signal pathways

Question 42

What are different forms of selectin?

Answer 42

L-selectin: found in white blood cells P-selectin: found in platelets E-selectin: expressed by endothelial cells; binds carbohydrates on white blood cells and platelets during inflammation

Question 43

What proteases help remodel the ECM?

Answer 43

matrix metalloproteases (MMPs) adamlysins merpins other proteinases (e.g. urokinase and tissue plasminogen activator)

Question 44

What are MMPs?

Answer 44

matrix metalloproteases secreted as zymogens and activated by other proteases or by thiol oxidation can degrade all components of the ECM natural inhibitors exist to regulate activity

Question 45

What are ADAMS?

Answer 45

adamlysins | sheddases that cleave the extracellular domains of cytokines and growth factor receptors

Question 46

What are Merphins?

Answer 46

involved in collagen cleavage | not well understood