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Cell Biology (BY1CB1) > Week 9 (Cytoskeleton- ECM & Cell Junctions) > Flashcards

Week 9 (Cytoskeleton- ECM & Cell Junctions) Flashcards

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1
Q

What is the Extracellular Matrix (ECM)?

A

The non-cellular extracellular component present within all tissues and organs

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2
Q

What are the functions of the ECM?

A

ECM provides not only an essential physical scaffolding for the cellular constituents, but also initiates crucial biochemical and biomechanical cues that are required for tissue morphogenesis, differentiation and homeostasis

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3
Q

Characteristics of ECM:

A
  • The classes of the ECM macromolecules in the ECM in different animal tissues are broadly similar. However, variations in the relative amounts of these macromolecules and in the ways in which they are organized differ
  • The ECM exists in different forms and texture depending on the location and function
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4
Q

Components of ECM:

•Glycosaminoglycans (GAGs):

A

large and highly charged, usually covalently linked to protein in the form of proteoglycans (~36)

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5
Q

Components of the ECM: Fibrous proteins

A

primarily members of the collagen family (~40)

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6
Q

Components of the ECM: non-collagen glycoproteins

A

carrying conventional asparagine-linked oligosaccharides, e.g. Fibronectin

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7
Q

What are the 3 main components of the ECM?

A
  • Glycosaminoglycans
  • Fibrous proteins
  • Non- Collagen glycoproteins
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8
Q

Components of the Extracellular Matrix- Collagens

A

Collagens:
• A family of fibrous proteins secreted in large quantities by connective-tissue cells
•Major component of skin (dermis) and bone
•Most abundant protein in mammals
•Extremely rich in proline and glycine

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9
Q

Extracellular Matrix- what are the main types of Collagens?

A 
Fibril-forming (Fibrillar)
Fibril-associated
Network-forming
Transmembrane
Proteoglycan core protein
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10
Q

Extracellular Matrix- Collagens Fibril-forming (Fibrillar):

A

➢Type I: Bone, skin, tendons, ligaments etc. (accounts for 90% of body collagen)
➢Type II: Cartilage, intervertegral disc etc.
➢ Type III: Skin, blood vessels, internal organs etc.
➢ Type V: Dermis, bone tendon etc.

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11
Q

Extracellular matrix: Fibril-associated Network forming

A

Network-forming: Sheet-like network and anchoring fibrils, e.g. Collagen IV

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12
Q

Extracellular matrix- fibril associated collagen: Transmembrane

A

Non-fibrillar, e.g. Collagen XIII

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13
Q

Extracellular matrix- fibril associated collagen:Proteoglycan core protein

A

Non-fibrillar

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14
Q

Extracellular Matrix- what are the cellular functions of Collagens?

A
  • Supporting cell adhesion, migration and differentiation
  • Regulating cell signalling
  • Entrapping growth factors and cytokines
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15
Q

Extracellular matrix: properties of collagens

A
  • Imparting support, strength, shape and elasticity to the tissues
  • Providing flexibility, support and movement to cartilage
  • Protecting delicate organs, such as kidneys and spleen
  • Wound healing
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16
Q

Extracellular matrix: Pathological conditions

A

•Genetic disorders

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17
Q

Extracellular Matrix- Elastin

A
  • Highly hydrophobic protein
  • Rich in proline and glycine
  • Not glycosylated
  • Secreted as tropoelastin (biosynthetic precursor of elastin)
  • Following secretion, tropoelastin molecules become crosslinked to one another to generate an extensive network of elastin fibers and sheets
  • The dominant extracellular matrix protein in arteries giving elasticity
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18
Q

Components of the Extracellular Matrix- Non-collagen glycoproteins:
Fibronectin (FN)

A

•A dimer composed of two very large subunits (MW 220,000) joined by disulfide bonds at their C-terminal ends.
• The Arg-Gly-Asp (RGD) sequence is important in regulating cell-ECM adhesion via interaction with integrins
• FN is important in fibrillar adhesions
- has different binding sites for other Extracellular proteins

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19
Q

Components of the Extracellular Matrix: Give examples of Glycosaminoglycans

A
  • Chondroitin Sulfate
  • Hyaluronan
  • Dermatan sulfate
  • Heparan sulfate
  • Keratan sulfate
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20
Q

Components of Extracellular Matrix- Properties of Basal Lamina

A

• Also known as basement membrane
• Thin, tough, flexible sheet of matrix molecules that is an essential underpinning of all epithelia
•Laminin and Type IV collagen are major components of Basal Lamina
➢ Laminin: heterotrimers of three long polypeptide chains (α, β and γ)
➢ Collagen IV: Network collagen
• Basal Lamina interacts with cell surface receptors, including integrins and dystronglycan that organize basal lamina assembly

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21
Q

Extracellular Matrix:

Functions of Basal Lamina

A
  • Separating epithelial cells and basement membrane resident cells from the underlying or surrounding connective tissue and forming the mechanical connection between them
  • Functioning as selective filter in the kidney glomerulus
  • Determining cell polarity
  • Influencing cell metabolism
  • Organizing the proteins in adjacent plasma membranes
  • Promoting cell survival, proliferation, and differentiation
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22
Q

What is cell adhesion?

A

Cell adhesion is the binding of a cell to a surface or substrate, such as an extracellular matrix or to another cell. Adhesion occurs from the action of proteins, called cell adhesion molecules, or sometimes adhesions.

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23
Q

What are the types of cell adhesion?

A

Cell-Extracellular Matrix (ECM) Adhesion

Cell-cell adhesion

24
Q

What are ligands?

A

A ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a signal-triggering molecule binding to a site on a target protein, e.g. receptor. The binding typically results in a change of conformation of the target protein.

25
Q

What is the functions of adherins?

A

Structural
Cell-cell or cell-matrix

They bind to actin filaments
( integrin-containing, multi-protein structures that form mechanical links between intracellular actin bundles and the extracellular substrate in many cell types)

26
Q

What are the functions of desmosomes?

A

Structural
Cell-cell

They bind to intermediate filaments and connect adjacent cells

27
Q

What are the functions of hemidesmosomes?

A

Structural
Cell-matrix

They connect the basal surface of epithelial cells via intermediate filaments to the underlying basal lamina

28
Q

What are the functions of focal adhesions?

A

Structural
Cell-matrix

They bind to actin filaments

29
Q

What are the functions of tight junctions?

A

Regulating transport between cells and along cell membrane
(Tight junctions are a type of cell-cell junction found in epithelia that forms a barrier that is impermeable to the majority of soluble molecules between the two sides of the epithelium.)

30
Q

What are the functions of gap junctions?

A

Cell-cell communication via ion and small molecule exchange

31
Q

Cell-cell adhesion: what are the different Cell Junctions?

A
  • desmosomes
  • tight junctions
  • gap junctions
32
Q

Cell-cell adhesion: Explain the functions of tight junctions

A

Tight junctions
•Seals gaps between cells to make them impermeable (e.g., intestine lung lining)
•Establishes polarity (apical/basal)
•Prevents backflow from one side of the epithelial layer to the next

33
Q

Cell-cell adhesions: explain the function of desmosomes

A

Desmosomes
•Connects the intermediate filaments of adjacent cells.
(Desmosomes form links between cells, and provide a connection between intermediate filaments of the cell cytoskeletons of adjacent cells- this provides strength)

34
Q

Cell-cell adhesion: what are Cadherins?

A 
Cadherins (named for "calcium-dependent adhesion") are a class of Type-1 transmembrane proteins. They play important roles in cell adhesion, forming adherin junctions to bind cells within tissues together.
Different types of cells express different cadherins, e.g. E-cadherin for epithelial cells, VE-cadherin for endothelial cells
35
Q

Cell-ECM adhesion: what are Integrins?

A

➢Integrins are one of the major players during cell-cell and cell-ECM adhesion
➢Integrins exist as heterodimers of two (α and β) non-covalently bound transmembrane glycoprotein subunits (including 18 α subunits and 8 β subunits). Different combinations bind to different ECM proteins.
➢Integrins are essential in many physiological processes during development and pathological conditions, such as cancer.
➢Integrins do not act alone during cell adhesion. They associate with ECM proteins, other cell surface receptors, intracellular signalling molecules and cytoskeleton components to mediate cell adhesion.

36
Q

Effects of ECM components such as fibronectin:

A

Integrins go through different stages during the cell adhesion process. This process is triggered by the interaction between integrins and ECM components, such as fibronectin

37
Q

Give an example of the pathological consequence of the loss of cell adhesion?

A

For example, the disastrous effects of loss of epidermal cell adhesion are epitomized by the life-threatening blistering skin diseases, such as pemphigus foliaceus and pemphigus vulgaris.

38
Q

What are pathological consequence of the loss of cell adhesion?

A

Pemphigus vulgaris is a rare autoimmune disease (autoantibody targeting desmosomes) that causes severe blistering of the skin and of the mucous membranes lining the mouth, nose, throat and genitals. The blisters have thin roofs and break easily to leave raw areas (erosions) that can be extensive and painful.

39
Q

What are the functions of Cell surface receptors e.g. Integrins, syndecans?

A 
Focal Adhesions
•Cell Adhesion (cell-cell and cell-ECM) and Cell Spreading
•Signal transduction
•Receptor recycling
•Protein secretion
•More to discover
40
Q

What are the ligand for Cell surface receptors

e.g. Integrins, syndecans?

A

ECM protein, e.g. Fibronectin, collagen, vitronectin, laminin etc. etc.
•Intracellular molecules, e.g. actin filaments

41
Q

What are the ligand for Cadherins?

A

Cell surface receptors

•Intracellular molecules, e.g. actin filaments

42
Q

What are the ligands for selectins?

A

Carbohydrates

43
Q

What are the ligands for Immunoglobulin (Ig) Superfamily (e.g. ICAM, NCAM)?

A

Integrins

44
Q

What are functions of Cadherins?

A

Cell-Cell adhesion
•Signalling transduction
•Receptor recycling
•More to discover

45
Q

What are functions of Selectins?

A

Circulating cells

•Rolling adhesion of white blood cells to endothelial cells

46
Q

What is the main type of connective tissue?

A

Fibroblasts

47
Q

Function of fibroblasts?

A

Synthesises the ECM and collagen

48
Q

Which amino acids play key roles in collagen stability?

A

Proline and hydroxyproline

49
Q

What is the main difference between collagen and elastin?

A

Elastin is not glycosylated

50
Q

CAMs- what is the function of the immunoglobulin superfamily

A

Immune response
Cell adhesion
Cell migration

Their ligands are Integrins

51
Q

What is the bent conformation of Integrins associated with?

A

Inactivity

52
Q

What is the extended, closed conformation of Integrins associated with?

A

Intermediate between active and inactive

53
Q

What is the open conformation of Integrins associated with?

A

Being active

54
Q

What is the functional part of actin?

A

F actin (forms polymers)

55
Q

Which subunit of Integrins has a greater binding affinity?

A

Beta subunit

56
Q

What happens if the cell-ECM adhesion is lost?

A

Cell death specifically termed anoikis
(RGD in fibronectin relased into extracellular environemnt and directly occupy integrin binding sites or other matrix proteins, cell no longer able to interact with ECM)

57
Q

What are the functions of the cytoskeleton?

A
  • Gives cell shape and mechanical resistance to deformation
  • Provides active contraction, thereby deforming the cell and the cell’s environment and allowing cells to migrate
  • Signalling transduction from stimuli
  • Uptake of extracellular materials (endocytosis)
  • Intracellular transportation
  • Forming special structures, e. g. lamellipodia
  • Cytokinesis
  • Mitosis

Cell Biology (BY1CB1) (16 decks)

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