Lecture 16 - From Cells to Tissues Flashcards

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1
Q

What does the ECM consist of?

A

Proteins and proteoglycans.

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2
Q

Functions of the ECM?

A
  1. Inert scaffold - stabilise the physical structure of tissues.
  2. Define the cellular phenotype of cells residing within the ECM.
  3. Acts as a storage compartment for cell signalling factors.
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3
Q

4 major components of the ECM?

A

Collagens, proteoglycans, elastin and fibronectin.

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4
Q

What are collagens composed of?

A

Composed of alpha chains that wrap into a triple helix. These trimers can either be homo- or heteropolymers.

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5
Q

AA sequence?

A

In the AA sequence glycine is every 3rd residue. The 1st and 2nd AA are either proline, hydroxyproline or hydroxylysine.

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6
Q

Vitamin C is an essential cofactor of collagens. Why is it important? A lack of VC can cause what?

A

It hydrolyses proline and lysine residues. A lack of VC can result in scurvy.

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7
Q

Main structural role of collagen?

A

To provide tensile strength to tissues, e.g. bone.

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8
Q

Order of structure formation for collagen fibres?

A

Alpha chains –> triple helix –> collagen fibrils –> collagen fibres.

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9
Q

Why is glycine AA important for the structure of collagen?

A

It is small - enables the twisting of chains.

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10
Q

The family of collagens is large and diverse. Name some similarities and differences between the subgroups.

A

Collagen I - different alpha helices.
Collagen II - homotrimer.
Similarity - they both form trimers.

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11
Q

Steps of collagen synthesis?

A
  1. Synthesis of pro-alpha chains via ribosomes. They are called pro-alpha chains because they have propeptides at the N termnius.
  2. Hydroxylation step - OH residues added to the proline/lysine.
  3. Glycosylation of alpha chain.
  4. Assembly of 3 pro-alpha chains.
  5. Pro collagen triple helix is secreted into the extracellular space.
  6. Propeptides cleaved. Collagen helix produced. Fibril –> fibre.
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12
Q

Mutations in the alpha 1(I) and alpha 2 (I) genes cause what disease?

A
Osteogenesis imperfecta (OI). Brittle Bone disease. 
Bones break easily, blueing of the sclerae of the eye.
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13
Q

Dermatosparaxis (inherited disorder) shows what symptoms?

A

Causes fragile/loose/hyperflexible skin with bruising and bleeding. Causes by a mutation in the N-terminal propeptidase called ADAMTS-2, means that it cannot remove the propeptides in type I and III collagen.

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14
Q

What does a proteoglycan consist of?

A

Glucosaminoglycans (GAGs) covalently attached to a core protein (except hyaluronan).

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15
Q

Name the four classes of GAGs.

A

Hyaluronan (HA), chondroitin sulphate (CS), heparin sulphate (HS) and keratin sulphate (KS).

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16
Q

Why is there a variety of proteoglycans?

A

Due to different combinations of the core protein with different proteoglycans. The number of GAG chains also affects function, e.g. decorin.

17
Q

Decorin vs aggrecan

A
Decorin = chondroitin sulphate and DS. Single GAG chain. Found in connective tissue. 
Aggrecan = chondroitin sulphate and keratin sulphate. Found in cartilage, mechanical support.
18
Q

How are proteoglycans synthesised?

A

Linking sugars (galactose - galactose -xylose) and glucoronic acid (GlcUA) enable the attachment of GAG repeats.

19
Q

Why is hyaluronan a unique GAG?

A

It binds to a proteoglycan through link proteins. Consists of repeating disaccharide units and its role is to link proteoglycans.

20
Q

How do proteoglycans regulate the strength of FGF signalling?

A
  • FGF ligand must bind to its PM receptor.
  • Syndecan is a PM proteoglycan that can protrude HS side chains.
  • FGF binds to HS –> close proximity to receptors.
  • HS proteoglycans are also found in the ECM.
  • FGF still binds, but in this instance the ligand is sequestered from its interaction with the receptor, reducing the strength of the FGF signal.
21
Q

Structure of elastin molecules?

A

Coiled to allow stretching, Covalently linked monomers.

22
Q

Multiple mutations in elastin can cause the rare inherited disorder called?

A

Curtis Laxa. Skin becomes elastic and hangs loosely. Hypermobility of joints.

23
Q

What is fibronectin and what is its function?

A

Large glycoprotein. Dimer, multiple different binding domains for proteoglycans, cells and collagen. Helps with matrix organisation.

24
Q

Where is the basal lamina found?

A

Between the dermis and epidermis of the skin.

25
Q

What is the basal lamina composed of?

A

Entactin, perlecan, laminin and type IV collagen. Form a flattened structure.

26
Q

How does collagen IV promote the flattened structure of the basal lamina?

A

It is a triple helix molecule with a globular head region that can form end-on-end and lateral (side by side) associations. Allows criss-cross association of the molecules, forming the unique planar structure.