Lecture 24: The Extracellular Matrix Flashcards Preview

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Flashcards in Lecture 24: The Extracellular Matrix Deck (52)
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1

General structure

2

The basal lamina

• 40-120 nm mat of extracellular matrix that underlies all epithelial sheets, also called the basement membrane 

• Serve structural and organization roles 

3

4 components of basal lamina

• Composed mainly of fiberous proteins and glycosyaminoglycans 

– Type IV collagen  

– Laminin 

– Nodulin 

– Perlecan (Heparan sulfate proteoglycan) 

4

Type IV collagen

• Similar to type IX collagen in that it is much more flexible than fibrillar collagen due to breaks in the helical structure 

• Pro-sequences are not removed and these terminal domains help form sheetlike multilayered networks

5

Functions of the basal lamina

structure, organization, filtration

6

Comparative size of major ECM components 

7

The structure of laminin

α-chains contain the “RGD” sequence that interacts with integrins

8

Model for basal lamina organization

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Function: filtration

– The basal lamina in kidneys serve as an additional filter preventing the passage a macromolecules from the blood into the urine 

10

Function: boundary formation

– Physically separates epithelial cells from underlying fibroblasts 

– Template for tissue reformation following injury 

• While the cell surrounded by the basal lamina may die, the basal lamina helps as a placeholder until new cells are regenerated. This the particularly import for muscle cells 

11

Basal lamina at the neuromuscular junction

12

Integrins

• Integral membrane proteins that link the cytoskeleton to the extracellular matrix 

• Can signal bidirectionally 

• Transmembrane heterodimers

• Can form transient structure like focal adhesions or stable, llong lived structures like myotendinous junctions 

• Capable of switching between active and inactive conformations 

13

____ link to the actin cytoskeleton though fibronectin in the ECM and talin and vinculin as intracellular anchor protein (Focal adhesions) 

integrins

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Integrins link to intermediate filament through ____ in the ECM and ____ and ____ as intracellular anchor protein (hemidesmosomes) 

laminin in the ECM and plectin and dystonin as intracellular anchor protein

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Integrin link to the actin cytoskeleton 

16

Hemidesmosome

Integrin links to intermediate filaments 

17

Integrins are activated through outside in signaling

Ligand binding induces a large conformational change in the extracellular domain, resulting in strong ligand binding. This change also triggers a lateral movement of the TMD apart that generates a strong talin binding site inside the membrane. This is “outside-in” signaling. The reverse “inside-out” signaling also occurs. 

18

Crosstalk from other signaling pathways can activate integrins, example of inside out signalling

19

Defects in integrins result in:

skin, muscle, blood disorders, or severe complications that lead to death of embryo

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Focal Adhesions

• Connect actin filaments to the basal lamina 

• Transmembrane adhesion proteins belong to the integrin family 

• Regulated assemblies that are altered during cellular movement 

21

____ regulates the number and stability of focal adhesions 

Focal Adhesion Kinase (FAK)

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Where is the extracellular matrix in this picture?

blue part

23

Primary ECM components 

• Polysaccharide chains 

– Glycosaminoglycans (GAGs) 

– Proteoglycans 

• Fibrous proteins 

– Collagen 

– Elastin 

– Fibronectin 

– laminin 

24

Fibroblasts in connective tissue are mainly made up of: 

Mainly collagen fibrils, no elastic fibers, glycoproteins, hylauronan, or proteoglycan that are normally present

25

Glycosaminoglycans (GAGs) 

• Unbranched polysaccharide chains composed of repeating disaccharide units 

• All GAGs contain an amino sugar (Nacetylglucosamine or N-acetyl galactosamine) and a uronic acid (iduonic acid or glucuronic acid) 

• Occupy a large amount of space 

• Form hydrated gels 

26

Four main groups of GAGs

– Hyaluronan 

– Dermatan sulfate and chondroitin sulfate 

– Heparan sulfate 

– Keratan sulfate 

27

Repeat unit of a Heparan sulfate glycoaminoglycan (GAG) chain 

Typically 70-200 sugars long. Shown fully sulfated. In vivo, the proportion of sulfated and non-sulfated is variable Heparin typically has >70% sulfate while heparan has <50%

28

Relative dimensions and volumes of various macromolecules 

• The stiffness of polysaccharides prevent them from folding into compact structures like proteins 

• Their charge can also attract counter ions, primarily Na+, causing large amounts of water to flow into them 

29

Hyaluronan 

• Also called hyaluronic acid or hyaluronate

• Simple GAG of repeating disaccharide units up to 25,000 sugars long

• Important lubricant in joints 

 

30

How is hyaluronan different from other GAGs

 • Unlike most other GAG, it does not contain sulfated sugars 

• Not linked to a protein cores 

• Not secreted like other GAGs, but is synthesized at the inner face of the plasma membrane and extruded out of the cell