Cell Biology Chapter 6 - The Extracellular Matrix and Cell Junctions

Question 1

What is the Extracellular Matrix?

Answer 1

is a Complex Network of Molecules that Fills the Spaces Between Cells in a Multicellular Organism

Question 2

Three essential properties of multicellularity…

Answer 2

1) They form stable bonds between neighboring cells.
2) As the number of cells in an organism increases, the material that fills the extracellular space plays an increasingly important role in governing the location and behavior of the cells.
3) The cells have a means of communicating with each other via cell-contact, or indirectly via signaling molecules that span extracellular spaces.

Question 3

Glycoproteins

Answer 3

form filamentous networks between cells

Sugar molecules can be attached to amino acids on proteins to generate
Glycoprotein (low abundance of sugar)
Proteoglycans (high abundance of sugar)

Extracellular Matrix contains both types of molecules

Question 4

Collagen

Answer 4

Family of glycoprotein that provides structural support to tissues

Question 5

Collagen characteristics

Answer 5

Collagen family of proteins are the most abundant in the animal kingdom

Nearly ALL animal cells synthesize and secrete at least one type.

Structural support

Tremendous strength

Question 6

Three Kinds of Collagen Structures

Answer 6

Fibrillar collagen – strength along a single axis
Sheet-like collagens – coiled coils in branched networks withstands stretching in multiple directions
Fibril-associated collagen forms coiled-coils that help bind Fibrillar collagens together

Question 7

Structure Of Collagen Fibers

Answer 7

Thin, triple helical coiled-coil
Abundance of noncovalent and covalent bonds
3 polypeptide subunits wrapped in parallel to form a 300-nm-long coiled coil
characteristic repeat sequence consisting of glycine-X-Y

Question 8

Four Major Classes of Collagen

Answer 8

1) Fibril forming eg. Bones, cornea, tendons, skin
2) Fibril-associated eg. Cartilage
3) network-forming eg. Basal lamina
4) Transmembrane eg. Hemidesmosomes

Question 9

Collagen Assembly

Answer 9

Fully assembled collagen is larger than the cells that make them
Collagen is made as coiled-coils with N- and C- termini covered in globular domains to prevent assembly
Travels from ER to Golgi to Plasma Membrane where it undergoes exocytosis
Enzymes cleave these domains so assembly can occur outside the cell

Question 10

Trafficking of Collagen

Answer 10

Collagen is too big for typical ER-Golgi-PM vesicles
A new compartment is generated
Called a vesicular tubular cluster (ER to Golgi transport)
At the Golgi, Collagen can be N- or O-glycosylated
Golgi to PM transport involves another new compartment
Elongated membrane-bound compartments called fibripositors

Question 11

Fibronectins

Answer 11

Connect Cells To Collagenous Matrices

Question 12

Fibronectins

Answer 12

Fibronectins are glycoproteins in nearly all animal connective tissues
Can be soluble or insoluble
Connect cells to the extracellular matrix in tissues, regulate shape and organization of cells, and helps to control cell behavior (development and wound healing)
Essential for Embryonic Development

Question 13

Structure of Fibronectin

Answer 13

Fibronectin repeats
Can bind collagen, proteoglycans and other fibronectins
Secreted by cells as a soluble dimer
Assembled into insoluble networks upon contact with integrins

Question 14

Elastin Fibers

Answer 14

Impart Flexibility to Tissues

Returns to original shape after being distorted or stretched
Blood vessels, lungs, skin
Ratio of collagen to elastin in tissues can regulate the flexibility and strength of

Question 15

Elastic Fibers

Answer 15

Elastin is organized into elastic fibers, which consist of a core region enriched in elastin proteins surrounded by a tough coating called a microfiber (or microfibrillar) sh

Question 16

Elastin Fiber Pathologies

Answer 16

Curtis laxa – a disease involving loss of elastin fibers in skin and connective tissues
Mild skin wrinkling to nearly undetectable amounts of elastin fibers; patients with little or no elastin cannot maintain tissue integrity and die in early childhood
Williams Syndrome – patients produce truncated forms of elastin that lack some crosslinking domains; poorly organized fibers
Narrowing of the arteries

Question 17

Laminins

Answer 17

Provide An Adhesive Substrate For Cells

3 polypeptide subunits wrapped together to form a triple helical coiled coil (a heterotrimer)
each subunit extends “arms” out from the coil giving rise to a cross-shaped structure
Connected by disulfide bonds

Question 18

Laminin Structure

Answer 18

Do not form fibrils!
Organized into web-like networks that resist tensile forces like stretching
Binding sites for cell surface receptors and other components of the ECM
20 different receptors identified for just Laminin-111

Question 19

Hyaluronan (HA)

Answer 19

Is A GAG Enriched In Connective Tissues

Does NOT couple to proteoglycan core
Instead, it binds to enormous complexes of secreted proteoglycans
Creates large, hydrated spaces in the EM of cartilage
Synthesized by transmembrane enzymes in the plasma membrane
Can also bind CD44, a cell surface receptor that helps control growth, differentiation and migration

Question 20

The Basal Lamina

Answer 20

Is A Specialized EM

Lies immediately adjacent to, and in contact with, many cell types
Contains proteins (collagen IV and nidogen) found only in this structure
Adopts distinct, sheet-like arrangement
“Basement membrane”

Question 21

Four Principal Functions of the Basal Lamina

Answer 21

1) Serves as a structural foundation underneath epithelial layers
2) Is a selectively permeable layer between epithelial compartments
3) Proteoglycans in this layer bind, immobilize and concentrate proteins (such as growth factors) from tissue fluid
4) Laminin proteins in basal lamina serve as neuronal guidance signals

Question 22

Most Integrins Are Receptors For EM Proteins

Answer 22

Bind to EM proteins and membrane proteins expressed on surface of other cells
Principal surface proteins for holding tissues together
Complex structure
Classified into 3 subfamilies based on β subunits

Question 23

Integrin Structure

Answer 23

α Chain is composed of a β-propeller and an I domain
Half of all known α subunits have the αI domain, which interacts with an adhesion site found in the β-subunit. This determines ligand specificity for these receptors

Question 24

Specialized Integrin Clusters Play Distinct Roles In Cells

Answer 24

Clusters classified into 5 types
Require calcium to work
Composition of cluster varies depending on type(s) of integrins in cluster, type of EM bound by integrins, degree of tensile strain imposed on cluster, location of cluster in cell, and type of cell in which cluster forms

Question 25

Specialized Integrin Clusters Play Distinct Roles In Cells

Answer 25

Clusters classified into 5 types
Require calcium to work
Composition of cluster varies depending on type(s) of integrins in cluster, type of EM bound by integrins, degree of tensile strain imposed on cluster, location of cluster in cell, and type of cell in which cluster forms

Question 26

Hemidesmosomes

Answer 26

contain α6β4 integrin and link to the IF network

cell surface junction found at basal surface of plasma membrane of epithelial cells

A lack of functional hemidesmosomes results in severe blistering of epithelial tissues and can be fatal

Question 27

Cells Adhere to One Another via Specialized Proteins and Junctional Complexes

Answer 27

junctional complex is made up of:
tight junction
adherens junction
desmosome

Question 28

Tight Junctions

Answer 28

Small contacts or “kisses” between lateral membranes of adjacent cells
Over 24 proteins identified in these contacts
3 types of transmembrane proteins found in the tight junction:
Claudins
Occludins
Junctional adhesion molecule (JAM)
Connects to Actin Filaments
Functions as a permeability barrier

Question 29

Tight Junctions

Answer 29

Mediate Paracellular Transport

Like a molecular sieve through which molecules are filtered as the cross epithelial and endothelial cell boundaries
Cutoff size for free diffusion is 4-40 angstroms
How can ions pass through instantaneously, but other solutes require minutes or even hours to cross this junction?

Question 30

Tight Junctions also Create Two Distinct Membrane Domains

Answer 30

Act like a fence for Membrane Proteins – helps establish cell polarity
Basal versus Apical sides of the cell
Different membrane proteins
aPKC, Par-3 and Par-6 help establish cell polarity
Different functions

Question 31

Adherens Junctions Link Adjacent Cells

Answer 31

Hold epithelial and endothelial cells together – resist stress
Located right beneath the tight junctions
Zonula adherens is the most well-known adherins junction

Question 32

Two Properties of Adherins Junctions

Answer 32

Homophilic Binding
They contain transmembrane receptor proteins known as cadherins that bind other cadherins on neighboring cells

Catenins link Adherins Junctions to Actin Filaments, which are linked to myosin.
Allows the cell to contract and change cell shape without collapsing

Question 33

Desmosomes are Intermediate Filament-Based Cell Adhesion Complexes

Answer 33

Thick accumulations of fibrils running across gap between two plasma membranes of epithelial cells

Fibrils terminate in electron-dense material on cytosolic side of plasma membrane

Electron-dense patches are connected to intermediate filaments in cytosol of each cell

Question 34

Gap Junctions Allow Direct Transfer Of Molecules Between Adjacent Cells

Answer 34

Facilitate the transfer of ions and small molecules between adjacent cells

Only known means of cell-to-cell transport for animal cells

Facilitate electrical coupling between cardiac myocytes

Connexons (Can be homo-oligomeric or hetero-oligomeric
- 6 connexin subunits

Question 35

Calcium-dependent Cadherins Mediate Adhesion Between Cells

Answer 35

Cadherin Superfamily

70 structurally-related transmembrane proteins
2 properties:
bind to calcium ions to fold properly (Ca, for calcium)
adhere to other proteins (adherin)

Question 36

Classical Cadherins

Answer 36

1) Transmembrane receptors with a single membrane-spanning domain, 5 extracellular domains on the amino end and a cytoplasmic carboxy tail.
2) Function as dimer clusters on the cell surface
3) Require calcium

4) α-catenin and β-catenin couple them to actin filaments
β-catenin bound to cadherins cannot be used in cell signaling

5) Genetic knockdown of E-cadherin is embryonic lethal
Role in development

Question 37

Calcium-Independent NCAMs Mediate Adhesion between Neural Cells

Answer 37

Function primarily as cell-cell adhesion receptors
Expressed ONLY in neural cells
Found at the junctions between neighboring calls in the CNS and in the PNS, especially in nerve fibers
Made in ER, post-translationally modified in Golgi
Polysialic acid (PSA) is the most significant modification. Negative charges project it outwards attracting cations and water molecules

Question 38

Selectins Control Adhesion Of Circulating Immune Cells

Answer 38

Selectins are selectively expressed on cells in the vascular system
L-selectin on leukocytes
P-selectin on platelets and cytokine-activated endothelial cells
E-selectin on endothelial cells
Function to facilitate movement of leukocytes out of bloss vessels and into inflamed tissues (extravasation)

Question 39

Elastin is elastic because:

Answer 39

Under no stress, it forms a globular protein held together by hydrophobic bonds; when stress is applied, these hydrophobic bonds break, and the protein elongates. When the stress is released, the hydrophobic bonds reform, collapsing the elongated protein in a globule.

Question 40

Proteoglycans are especially abundant in articular cartilage (e.g., in the shoulder, hip, knee) because:

Answer 40

) Proteoglycans help cells resist compressive force by attracting water

Question 41

Which statement most accurately describes the difference between tight junctions and gap junctions?

Answer 41

Tight junctions block the transport of most extracellular materials between adjacent epithelial cells; gap junctions allow direct transfer of intracellular materials between adjacent epithelial cells.

Question 42

What property is shared by desmosomes and hemidesmosomes?

Answer 42

They both bind to intermediate filaments

Question 43

Macular degeneration
The following question refers to a common form of blindness in the elderly called age-related macular degeneration (AMD). One of the major problems in AMD patients is that a critical part of the eye called the retinal pigment epithelium (RPE) detaches from its underlying basal lamina, also called “Bruch’s membrane” or the “basement membrane.” The following is taken from the summary of a research article published in 2009 in Experimental Eye Research:
“Transplantation of retinal pigment epithelium (RPE) has been attempted in patients with age-related macular degeneration (AMD). However, inability of transplanted RPE to initially attach and subsequently proliferate on the basal lamina (Bruch’s membrane) may lead to failure of RPE transplants and poor visual outcomes. Integrin alpha(6)beta(4) functions as a receptor for laminin, the major component of Bruch’s membrane, and mediates the stable attachment of most epithelial cells to the underlying basement membrane. To improve adhesion and proliferation of transplanted RPE on Bruch’s membrane, we investigated whether transfer of the genes for integrin alpha(6) and beta(4) in RPE could promote adhesion and proliferation of transplanted RPE on Bruch’s membrane… Modification of integrin expression by transfection of these integrin genes into RPE cells induced a significant increase in cell adhesion to laminin

Answer 43

The hemidesmosome

Question 44

What property do collagens, laminins, and nuclear lamins share?

Answer 44

They have coiled coils containing alpha helices

Question 45

Which one of the following most accurately describes tight junctions?

Answer 45

They allow adjacent epithelial cells to control the passage molecules between them

Question 46

What property of gap junctions makes them different from all other cell surface structures?

Answer 46

They form hollow channels that connect the cytosol of two cells together

Question 47

Which statement best describes a cadherin?

Answer 47

) It is a transmembrane receptor in a cell-cell junction

Question 48

What makes elastin so elastic?

Answer 48

) It is made up of alternating regions of hydrophobic and hydrophilic amino acids that spontaneously refold after tensile stress is released

Question 49

What does the protein laminin do?

Answer 49

) It forms a network that confers structural stability to basement membranes (aka basal lamina)

Question 50

Which statement best describes the difference between a proteoglycan and a glycoprotein?

Answer 50

Which statement best describes the difference between a proteoglycan and a glycoprotein?

Question 51

Collagen is similar to intermediate filaments in forming relatively stable structures because:

Answer 51

Their subunits form coiled-coils.

Question 52

Which of the following statements about integrin receptors is false?

Answer 52

They are used to form desmosomes

Question 53

Which term does not belong with the others?

Answer 53

A) glycosaminoglycans 
 B) proteoglycans 
 C) collagen 
 D) hyaluronan 
 E) heparan sulfate 
Points Earned:	1.0/1.0	
Correct Answer(s):	C

Question 54

__________ attach the extracellular matrix to the cytoskeleton and intracellular signaling molecules.

Answer 54

Integrins

Question 55

Patients who have missing __________ display blistering of the skin.

Answer 55

desmosomes

Question 56

What structural feature makes desmosomes different from other cell-cell junctions in epithelial cells?

Answer 56

) They bind to intermediate filaments

Question 57

Elastin is an especially useful molecule, in that it imparts elasticity to tissues without the need for any metabolic energy. How does it work?

Answer 57

) It contains clusters of hydrophobic amino acids that spontaneously coil in the absence of mechanical strain, and the hydrophobic bonds stabilizing the tertiary structure of these amino acids are easily broken by mechanical stress

Question 58

In Jeopardy® format) This extracellular protein contains both hydrophobic and hydrophilic domains and is capable of spontaneously refolding after it has been extended.

Answer 58

What is elastin?