MCM 2-10: Tissue Organization, Cell Junctions, and Extracellular Matrix

Question 1

General organization and function of major tissue types

Answer 1

Cellular - tissue composed mainly of cells. integrity and properties are derived from cell junctions (epithelium)

Connective - tissue composed mainly of ECM with a few cells that synthesize, remodel, and bind the ECM. Physical properties of tissue is provided by organization of ECM (loose CT, cartilage, bone, tendon)

Question 2

what are anchoring/adhering junctions?

Answer 2

junctions whose primary purpose is to maintain tissue integrity under mechanical stress.

can be cell-cell or Cell-ECM junctions

Question 3

Three components of anchoring/adhering junctions

Answer 3

transmembrane glycoprotein - anchoring portion

complex of linker proteins on cytosolic face - regulates assembly and connects to cytoskeleton

cytoskeleton - connection can be to intermediate filaments or microfilaments (actin). Distributes force due to mechanical stress over a large area, allow the glycoprotein to stay attached.

Question 4

Four types of anchoring junctions

Answer 4

1. adherens junctions/zonula adherens
2. Focal Adhesions/Focal Contacts -
3. Desmosomes -
4. hemidesmosomes

Question 5

Tight Junctions/Zona Occludes (5 features)

Answer 5

1. provide permeability layer across epithelial sheets like in small intestine - This allows regulated transport of nutrients through the cells (Transcellular transport). Na+2 dependant uptake occurs at apical membranes, faciliatated diffusion occurs at basolateral membranes
2. maintain cell polarity by keeping membrane trasnport proteins in correct locations
3. claudin and occludin are major proteins of tight juncctions
4. strings of transmembrane proteins interact with each other on adjacent cells via homophilic interactions
5. cytoskeleton not needed for integrity

Question 6

Gap Junctions ( 3 features)

Answer 6

1. Provide means of communication between neighboring cells (such as electrical conduction in cardiac cells). Also known for passage of small molecules such as amino acids and vitamins
2. made of single protein called connexin. six connexin molecules associate in PM to form connexon (hemi channel). connexons on adjacent cells associate to form gap junctions
3. regulated by intracellular Ca+2 concentration or pH

high Ca+2 or low pH = gap junction close
low ca+2 or high pH = gap junction opens

Question 7

three major families of extracellular matrix proteins

Answer 7

fibrous proteins, bulky space filling proteins, cross linking proteins

Question 8

fibrous proteins

describe each type.

Answer 8

includes collagens (fibrillar, and type IV) and elastin

Fibrillar collagen provide tensil strength; resist stretching.
the pro-collagen triple helix is secreted from golgi and collagenases cleave the pro-peptides forming true collagen helices which then self associate into fibrils and fibers like tendons.

type IV collagen does not follow same pathway - when excreted into ECM it is not acted upon by collagenases, it forms mesh which is compoenet of basal lamina

Elastin provides elasticitiy. undergoes extensive cross linking following secretion via coalent linking of serine residues. elastic character is derived mostly from the many random coils in the polypeptide chain due to high proline content. The Glycoprotein fibrillin forms a sheath around the elastin fibers, preventing overstretching.

Question 9

bulky space filling proteins

includes what?

does what?

Answer 9

including proteoglycans.

Resist compression forces and allow for rapid diffusion of soluble molecule like growth factors.

also permit cell migration

the GAGS on proteoglycans have many sulfate and carboxyl groups, giving them negative charges making them hydrophilic. they can bind noncovalently many water molecules

a hydrated gel is only 10% proteoglycan.

Using linker proteins, proteoglycans can complex with hyalauronic acid and resist compression forces

in loose CT, primary role of proteoglycan molecules is structure and space filling, permitting free movement of water soluble molecules as well as cells in the matrix

Question 10

cross linking proteins

Answer 10

includes fibronectin and laminin.

Fibronectin - heterodimer that can assemble higher order structures. Many alternative-splice variants have modified functions. They have multiple binding sites giving them their functionality as crosslinking molecules. Fibronectin can bind :integrins, heparin, syndecan, types I,2,3 collagen, and fibrin

Laminin - a three chain polypeptide, forms component of basal lamina along with type 4 collagen and proteoglycan.
Laminin binds integrins on cell surface, heparin, TYPE 4 COLLAGEN

Question 11

Anchoring junction diseases

Answer 11

result in loss of tissue binding and blistering, can be fatal
-pemphigus - autoimmune, antibodies generated against cadherins, disrupt cell-cell junctiojns

-epidermylosis bullosa simplex - defect in keratin assembly

Question 12

Extracellular matrix protein diseases

Answer 12

ehlers-danlos - various fibirllar collagen defects, hyperextensible skin and joints

marfan syndrom - mutation in fibrillin gene, makes aorta prone to rupture

DMD - basal lamina plays role, as it surrounds and supports muscle cells

Question 13

adherens junctions/zonula adherens

Answer 13

• cell-cell anchoring junctions
• transmembrane glycoproteins are cadherins which require Ca+2 to interact with another cadherin on adjacent cell (homophilic).
• linker proteins interact with actin filaments

Question 14

Focal Contacts

Answer 14

• cell to ECM anchoring junctions
• TM glycoproteins are integrins (formed from alpha-beta subunit heterodimer) require Ca+2 to interact with fibronectin in the ECM (heterophilic)
• linker proteins interact with actin filaments

Question 15

desmosomes

Answer 15

Cell:Cell anchoring junctions

• tm glycoproetins are caherins (like adherins junctions)
• linker proteins interact with IF like keratins
• they connect IF filaments across epithelial sheet

Question 16

hemidesmosomes

Answer 16

cell: ECM anchoring junctions
- TM glycoproteins are integrin a6/b4 - attatch the of basal lamina
- linker proteins interact with IF
- connect intermediate filaments across an epithelial sheet

Question 17

The two Cell:Cell Adhering/anchoring junctions and what they have in common

Answer 17

Adherens junctions and Desmosomes

• cadherin glycoprotein
• homophilic interaction (cell to cell)

cell:cell are homophilic interactions with cadherin glycoproteins

Question 18

The two cell:ECM adhering/anchoring junctions and common features

Answer 18

Focal adhesions and Hemidesmosomes

• integrin glycoprotein
• heterophilic (cell:ECM)

Cell:ECM are heterophilic interactions with integrin glycoproteins

Question 19

the cytoskeleton of the 4 anchoring junctions

Answer 19

Adherens and Focal = Actin

Desmosomes and Hemidesmosomes - Intermediate filaments

Question 20

what do adherens junctions do?

Answer 20

provide strength and are important in development

Question 21

what do focal adhesions do?

Answer 21

orient contracts, important in developmental processes

Question 22

what do desmosomes do?

Answer 22

maintain cellular tissue integrity

Question 23

what do hemidesmosomes do?

Answer 23

maintain cellular tissue integrity

Question 24

describe the ECM

Answer 24

major component of CT, giving CT strength and integrity

-generated by fibroblasts, Chondroblasts(cartilage) or osteoblasts (bone)

Question 25

three major families of ECM proteins

Answer 25

fibrous proteins, bulky space filling proteins, cross-linking proteins

Question 26

fibrillin?

Answer 26

a glycoprotein which surrounds the fibrous protein elastin to prevent overstretching

Question 27

the crosslinking proteins fibronectin and laminin bind what?

Answer 27

fibronectin bind integrins (focal adhesions and desmosomes), heparin (GAG), syndecan (proteoglycan), 1/2/3 collagen, fibrin (blood clotting)

laminin - integrins on cell surface, heparin (GAG), type 4 collagen

Question 28

pemphigus

disease type?

Answer 28

Anchoring Junction Disease - An autoimmune disease in which antibodies are generated against cadherins, disrupting cell-cell junctions leading to a loss of tissue integrity/blistering

Question 29

Epidermolysis Bullosa Simplex –

disease type?

Answer 29

Defect in keratin assembly. anchoring junction disease

Question 30

Ehlers-Danlos syndrome

disease type?

Answer 30

– Various fibrillar collagen defects. Causes hyper extensible skin and joints.
– Mutation in the fibrillin gene. Makes the aorta prone to rupture.

ECM protein disease

Question 31

DMD?

disease type?

Answer 31

The basal lamina plays a role in DMD, as it surrounds and supports muscle cells.

ECM protein disease

Question 32

describe the basal lamina

makeup?

function?

Answer 32

proteogylcan + laminin + Type 4 collagen

Basal lamina is specialized ECM that

1. forms a dense meshwork that surrounds/supports muscle cells
2. links muscle to tendon
3. provides support for epithelial sheets
4. acts as molecular filter for the kidney
5. is involved in guidance pathways (neural crest cells).

Question 33

Which of the following junctions
DO NOT utilize interactions with the cytoskeleton in fulfilling their primary function?

A. Tight junctions only
B. Adherens junctions only
C. Gap junctions only
D. Gap junctions and adherens junctions
E. Gap junctions and tight junctions

Answer 33

E. Gap junctions and tight junctions

Question 34

loss of blood proteins into the urine is prevented primarily by?

A. The barrier function of the endothelial cell layer of the capillaries.
B. The basal lamina between the endothelium of the blood vessel and the glomerulus epithelium.
C. The glomerulus epithelium.
D. The connective tissue surrounding the capillary bed.
E. Adhesio
n of blood prot
eins to circulating platelets.

Answer 34

the basal lamina between the endothelium of bv and the glomerulus epithelium (Choice B)

Question 35

(2 pts) Which of the following extracellular matrix molecules is primarily responsible 
for the 
“shock absorbing” properties of cartilage?
A. Fibronectin
B. Proteoglycan
C. Type IV collagen
D. Laminin
E. Elastin

Answer 35

Proteoglycan - has gags with - residues. can bond water and form gel.

Question 36

Cleavage of the pro-peptides from type I collagen molecules occurs in the Golgi apparatus and is necessary for fibril formation.
TF

Answer 36

False - post translational modifications occur in the golgi forming a pro-collagen triple helix. When it is excreted, collagenases in the ECM cleave its pro peptides to form a true helical collagen