Lecture 18: Extracellular Matrix

Question 1

What is the ground substance of the extracellular matrix made of

Answer 1

Proteoglycans

Question 2

What are some qualities of collagen?

Answer 2

-highly interactive
-very stable
-EDS

Question 3

What is elasticity

Answer 3

the ability to return to its original shape.

Question 4

_________________:
-lung tissue needs elasticity to return to its original size on every respiratory cycle
-Lung tissue prevents degradation by releasing this hormone.
-2%-5% of emphysema patients in the US have this difficency

Answer 4

alpha 1 antitripsin deficiency

Question 5

___________________________:
* The extremely high number of negative charges
attract cations (Na+) surrounded with water.
* This generates a balance between chemical forces
bringing water into the ECM, and physical forces
pushing it out.

Answer 5

Shock amortization by GAGs

Question 6

Physical compression of the tissue displaces the water allowing for it to function as a ____________________

Answer 6

hydraulic cushion
*when the force is removed, water returns to the tissue and shape is recovered

Question 7

_______________ degenerative condition of joint cartilage (most often knees and hips may be affected)

Friction/damage –> inflammation –> more damage
Treatment is usually symptomatic

Answer 7

osteoarthritis

Question 8

What are some new treatments for osteoarthritis

Answer 8

New therapies using glucosamine sulphate and chondroitin sulfate have promising results in reducing pain and advancement of the disease

Question 9

• We will consider cell-matrix and cell-cell adhesion.
  _____________ have extracellular domains folded like an
  immunoglobulin domain (orange).

Answer 9

IgCAMs

Question 10

____________ domains (maroon) typically bind the same class of cadherin on a neighboring cell. Ca 2+ stabilizes the interaction. Cytoplasmic tails bind cytoskeletal adapter proteins.

Answer 10

CAD (cadherin)

Question 11

_______________are heterodimers of one α (out of 16 varieties) and one β (out of 8) subunits. They bind a wide range of matrix molecules.

Answer 11

Integrins

Question 12

_____________ have a Ca 2+ -dependent lectin (carbohydrate-
binding) domain (green), an epidermal growth factor (EGF)-like domain (blue), and a variable number of complement regulatory domains (red).

Answer 12

Selectins

Question 13

___________ use multiple carbohydrates for interactions with other cells.
* These receptors are anchored by a single transmembrane helix anchor.
* Adapter proteins link the cytoplasmic tails of most adhesion

Answer 13

Mucins

Question 14

What are the principles of cell adhesion?

Answer 14

1. Cell adhesion is determined by selective expression of adhesion molecules
2. Many adhesion proteins bind one ligand, and many ligands bind only one type of receptors. Some receipts do not follow this
3. Adhesion can be regulated by surface density, state of aggregation and state of activation of adhesion receptors
4. Ligand affinity is low leading to fast dissociation and rapid reversal of interactions
5. Many additional receptors connect with the cytoskeleton and transduce force and tension from the envirnment
6. Ligand binding activities intracellular pathways

Question 15

1 to 7 _______________ are anchored to the plasma membrane by a single transmembrane helix

Answer 15

extracellular immunoglobulin domain

Question 16

__________ is cytoplasmic and interacts with intracellular ligands including tyrosine kinases and adaptive proteins with pectin to actin filaments

Answer 16

C terminus

Question 17

__________ are used in neural development for synapses and myelin sheet formation

Answer 17

IgCAMs

Question 18

___________ interaction with blood cell integral is needed for adhesion and extravasation in response to inflammation

Answer 18

ICAM1

Question 19

What does Cadherin Stand for

Answer 19

Calcium dependent adhesion proteins

Question 20

Which Cadherin proteins are homophilic and heterophilic

Answer 20

Homophilic: bind to same cadherin on neighboring cells
Heterophilic: bind to other types of cadherin

Question 21

What regions of the cell are rich in homophilic cadherins

Answer 21

Specialized cell-cell junctions

Question 22

In terns of chagrin signaling what is contact inhibition?

Answer 22

Cell-cell interactions signal cellular crowding and inhibit migration and proliferation

Question 23

E cadherin can contribute to ____________

Answer 23

malignancy

Question 24

________________ regulates cell proliferation and is inhibited by the Wnt pathway, which lead to the digestion of B cathenin

Answer 24

free intracellular B cathenin

Question 25

The _____________ is a tyrosine kinase receptor. Over activation by mutations that cause dimerization causing cancer.

Answer 25

Cadherin RET

Question 26

Deficiency in Cadherin RET causes

Answer 26

Hirschsprung disease in which autonomic nerves in the wall of the intestines fail to develop causing sever dysfunction

Question 27

What is the function of cadherin proteins in embryo development

Answer 27

The ability of cadherins to keep cells with similar cadherins together helps in organization of embryonal tissues

Question 28

___________ are the main cellular receptors for EXM molecules but some bind adhesion molecules on other cells

Answer 28

integrins

Question 29

Integrins bind ______________________________ providing physical attachments necessary to transmit internal forces to the matrix and resist external forces

Answer 29

epithelial and muscle cells to laminin in the basal lamina

Question 30

These interactions of ligand with _____________ also generate signals that control cell growth and structure

Answer 30

integrins

Question 31

Intracellular binding primes for ___________________

Answer 31

extracellular ligands

Question 32

_________________
* Approximately one-third of matrix ligands for integrins involve the sequence
motif RGD (arginyl-glycyl-aspartic acid) or other simple sequences in otherwise
unrelated proteins. -> They can bind multiple ligands.
* For example, fibronectin binds to at least nine different integrins, and both
laminin and von Willebrand factor bind at least five different integrins.

Answer 32

Extracellular ligands

Question 33

Affinity for ligands is low, allowing for __________________

Answer 33

fast dissociation and cell movement

Question 34

Integrins cluster together in ___________

Answer 34

focal contacts.

Question 35

Adapter proteins ______________ link conserved binding sites on the cytoplasmic domains of β-integrins directly to actin filaments at the ends of stress fibers.

Answer 35

talin and vinculin

Question 36

• Activation of talin by PIP2 (Phosphatidyl Inositol bisPhosphate) induces extension of _____________ to facilitate extracellular binding.

Answer 36

Integrins

Question 37

_____________ is an adaptor for signaling proteins, such as SRC protein kinases and focal adhesion kinases.

Answer 37

Paxilin

Question 38

Cytoplasmic proteins ____________ activate interns by binding the cytoplasmic tail of the Beta integrin and separating the two transmembrane domains

Answer 38

Talin and kindlins

Question 39

______________ bind to glycoproteins and mucins, particularly important in immune cell migration and embryo implantation

Answer 39

Selectin Family

Question 40

___________ primarily bind to selectins, abundant negative charges in their glycan groups allow them to extend far from the cell surface.

Answer 40

Mucin Family