The extracellular matrix of animal connective tissues

Question 1

The classes of macromolecules that constitute the ECM are broadly similar, but it is the variation in their ___________and their _________ that give rise to diversity of tissues.

Answer 1

Relative amounts, organization

Question 2

The ECM can become

Answer 2

can become calcified to become bone or teeth or it can become the transparent substance of the cornea or the rope-like organization of tendons

Question 3

Matrix molecules are secretes by cells called

Answer 3

fibroblasts

Question 4

In certain specialized connective tissues such as cartilage and bone, fibroblasts have specific names such as ________ and ________, respectively.

Answer 4

Chondrocytes, osteoblasts

Question 5

The matrix in connective tissue is constructed from the same two main classes of macromolecules as in basal laminae:

Answer 5

1) glycosaminoglycan (GAG) polysaccharide chains usually covalently linked to proteins in the form of proteoglycans
2) fibrous proteins such as collagen.

Question 6

Polysaccharides

Answer 6

resists compressive forces on the matrix while permitting rapid diffusion of nutrients, metabolites, and hormones between the blood and tissue cells

Question 7

Collagen fibers

Answer 7

strengthen and help organize the matrix, while other fibrous proteins such as elastin (rubber-like) give it resilience.

Question 8

Major protein of the extracellular matrix

Answer 8

Collagens

Question 9

Collagens are secreted in large quantities by _______ and small quantities by _______

Answer 9

Connective tissue cells, many other cell types

Question 10

What is the principal collagen of skin and bone

Answer 10

Type I collagen

Question 11

After being secreted into the extracellular space, these collagen molecules assemble into higher order polymers called

Answer 11

collagen fibrils

Question 12

Primary feature of a typical collagen molecule

Answer 12

its long, stiff, triple-stranded helical structure, in which three collagen polypeptide chains called α chains are wound around one another in a rope-like superhelix.

Question 13

What are collagens extremely rich in that are found every 3rd a.a

Answer 13

Glycine

Question 14

What does glycine allow for

Answer 14

allows the three helical α chains to pack tightly together to form the final collagen superhelix

Question 15

What is found under the fibroblast cell

Answer 15

Long strands of collagen fibrils

Question 16

Post-translational modifications collagen chains undergo

Answer 16

Individual collagen polypeptide chains are synthesized on membrane-bound ribosomes and injected into the lumen of the rough endoplasmic reticulum as large precursors called pro-α chains. After being trimmed, hydroxylated and glycosylated, each pro-α chain then combines with two others to form the triple-stranded, helical procollagen

Question 17

________ and ________ are infrequently found in other animal proteins

Answer 17

Hydroxylysines and hydroxyprolines

Question 18

What gives tissues their elasticity

Answer 18

Elastin

Question 18

Vertebrate tissues need to be both ______ and ______

Answer 18

strong, elastic

Question 19

What makes vertebrate tissue strong and elastic

Answer 19

Strong: collagen
Elastic: elastin

Question 20

A network of elastic fibers in the ECM of these tissues
gives them the required __________- so that they can recoil after transient stretch.

Answer 20

Resilience

Question 21

How is stretching and tearing limited

Answer 21

Long, non-elastic collagen fibrils are interwoven with elastic fibers

Question 22

Like collagen, elastin is

Answer 22

unusually rich in proline and glycine

Question 23

Unlike collagen, elastin is

Answer 23

not glycosylated and contains hydroxyproline but not hydroxylysine

Question 24

The precursor of elastin

Answer 24

Soluble tropoelastin

Question 25

How are elastic fibers assembled at the PM?

Answer 25

Soluble tropoelastin is secreted into the extracellular space and assembled into elastic fibers

Question 26

What happens after secretion of tropoelastin

Answer 26

Tropoelastin becomes highly crosslinked to one another between lysines

Question 27

The elastin protein is composed largely of WHAT two types of short segments that alternate along the polypeptide chain

Answer 27

1). hydrophobic segments which are responsible for the elastic properties 2 alanine- and lysine-rich alpha-helical segments which form cross-links between adjacent molecules

Question 28

Fibronectin

Answer 28

an extracellular protein that helps cells attach to the matrix

Question 29

The ECM contains a number of

Answer 29

non-collagen proteins with binding sites for other matrix macromolecules and for cell-surface receptors

Question 30

Fibronectin is found where an is important for

Answer 30

large glycoprotein found in all vertebrates and important for many cell-matrix interactions

Question 31

What happens to mice that cant synthesize fibronectin

Answer 31

die early in embryogenesis because their endothelial cells are unable to form proper blood vessels.

Question 32

Fibronectin is a dimer composed of

Answer 32

two very large subunits joined by disulfide bonds at one end

Question 33

What regulates the assembly of fibronectin fibrils

Answer 33

Tension exerted by cells

Question 34

Fibronectin in soluble form

Answer 34

Circulates in the blood and other bodily fluids

Question 35

Fibronectin in insoluble form

Answer 35

Fibronectin dimers are cross-linked to one another by additional disulfide bonds in the ECM

Question 36

Difference between fibrillar collagen and fibronectin molecules (form and assembly)

Answer 36

Fibrillar collagen can form fibrils in test tubes alone, fibronectin molecules only assemble into fibrils on the surface of cells and only where the cells possess appropriate binding partners such as integrins

Question 37

Integrins provide

Answer 37

A linkage from the fibronectin outside of a cell to the actin cytoskeleton inside

Question 38

Fibronectin binds to cells through an

Answer 38

RGD motif that bind integrins

Question 39

What molecules assemble into fibrils where cells possess integrins or binding partners

Answer 39

Fibronectin

Question 40

The ability to cut through the matrix is crucial in two ways

Answer 40

1) it enables cells to divide while embedded in the matrix; 2) it enables them to travel through it

Question 41

Matrix degradation is exploited by __________ to spread through the body

Answer 41

Cancer cells

Question 42

Cells degrade matrix components through extracellular ___________ that act close to the cells that produce them

Answer 42

cancer cells

Question 43

Many of these proteases belong to one of two general classes:

Answer 43

* 1) matrix metalloproteases, which depend on bound Ca 2+ and Zn2+ * 2) serine protease, which have a highly reactive serine in their active site

Question 44

Some are highly specific and only cleave particular proteins in a few sites such as _________

Answer 44

collagenases

Question 45

Less specific proteases

Answer 45

Act just where needed as they are anchored to the plasma membrane

Question 46

We can restrict the breakdown of the ECM by

Answer 46

1. Having the protease be very specific in which type of ECM it is going to break down 2. Limit its location by anchoring the protease to a specific structure

Question 47

Local activation

Answer 47

Many proteases are secreted as inactive precursors that can be activated when needed. Plasminogens are inactive proteases in the blood that, when cleaved by plasminogen activators, yield the active protease plasmin which helps break up blood clots.

Question 48

Confinement by cell-sruface receptors

Answer 48

Many cell-surface receptors bind to proteases confining the enzyme to where it is needed. An example is urokinase plasminogen activator which is found at the leading edge of migrating cells. (limited by location)

Question 49

Secretion of inhibitors

Answer 49

Secreting protease inhibitors such as tissue inhibitors of metalloproteases (TIMPs) and the serine protease inhibitors known as serpins.

Question 50

The matrix exerts powerful influences on the cells through

Answer 50

Transmembrane cell adhesion proteins that act as matrix receptors

Question 51

The principal receptors on animals cells for binding most ECM proteins are the

Answer 51

Integrins

Question 52

Integrins bind

Answer 52

Laminins and fibronectins

Question 53

Integrins (large family of transmembrane adhesion molecules) have the ability to

Answer 53

transmit signals in both directions across the cell membrane

Question 54

Integrins are _______ that link to the cytoskeleton

Answer 54

Transmembrane heterodimers

Question 55

An integrin molecule is composed of

Answer 55

Two non-cavalently associated glycoproteins called alpha and beta

Question 56

Integrin: The __________ portion binds to ECM proteins such as laminin or fibronectin, or to ligands on the surface of other cells

Answer 56

Extracellular

Question 57

Integrins: the intracellular portion binds to _______ via

Answer 57

Binds to actin via the protein talin and a set of anchorage proteins

Question 58

True or false: integrins can switch between an active and an inactive conformation

Answer 58

True

Question 59

What does a cell crawling through a tissue have to be able to do

Answer 59

has to be able to make and break attachments to the matrix and to do so rapidly if traveling quickly.

Question 60

If force is to be applied where it is needed, the making and breaking of attachments has to be

Answer 60

coupled to the assembly and disassembly of cytoskeletal attachments inside the cell.

Question 61

As an integrin binds to or detaches from its ligands, it undergoes _________________ that affect both the intracellular and the extracellular end of the molecule.

Answer 61

conformational changes

Question 62

Outside-in integrin activation

Answer 62

Stimulus binds to the RGD domain of fibronectin, inducing a structural change that causes the talin binding domain to be revealed which allows the integrin (and ECM via fibronectin) to be linked to the cytoskeleton inside the cell

Question 63

Talin links

Answer 63

The integrin to the cytoskeleton

Question 64

Inside-out integrin activation

Question 65

In _________ and ______, the ability to regulate integrin activity via inside-out signalling is particularly important

Answer 65

White blood cells, platelets

Question 66

Repeated adhesion allows

Answer 66

A cell to circulate unimpeded until it encounters an appropriate stimulus

Question 67

True or false: Integrins do not need to be synthesized de novo therefore the signal is rapid

Answer 67

True

Question 68

True or false: In inside-out integrin signalling, the signal could still have originated from outside the cell BUT the activation of the integrin specifically is going in an inside out order

Answer 68

True

Question 69

Inside-out signalling PIP2

Answer 69

PIP2 activated Talin, Talin binds b-integrin, conformational change to open integrin, binds ECM

Question 70

Integrins differ from RTK's in that

Answer 70

they bind their ligand with lower affinity and are therefore more abundant (10-100-fold) at the cell surface

Question 71

The Velcro principle

Answer 71

Many receptor ligand interactions give increased strength to the adhesion between cell and ECM --> multiple low affinity bonds cause higher strength

Question 72

ECM attachments act through ________ to control cell proliferation and survival

Answer 72

Integrins

Question 73

Integrins activate ______________ to allow a cell to behave according to its surrounding matrix

Answer 73

Intracellular signalling pathways

Question 74

What happens when cells lose contact with their ECM

Answer 74

They initiates apoptosis ANCHORAGE-DEPENDENCE

Question 75

FAK is recruited by

Answer 75

intracellular anchor proteins such as talin

Question 76

How is docking site for the Src family of tyrosine kinases (Fyn)

Answer 76

The clustered FAK molecules cross-phosphorylate each other on a specific tyrosine

Question 77

What does FAK do

Answer 77

FAK helps disassemble focal adhesions

Question 78

Outside-in signaling is relayed from integrins, via _____ and ________- kinases into the cell.

Answer 78

FAK and Src-family kinases

Question 79

Mutant mice lacking FAK

Answer 79

their fibroblasts still adhere to fibronectin and form focal adhesions. But they form too many focal adhesions and do not migrate