Lecture 24: The Extracellular Matrix Flashcards Preview

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


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 


4 components of basal lamina

• Composed mainly of fiberous proteins and glycosyaminoglycans 

– Type IV collagen  

– Laminin 

– Nodulin 

– Perlecan (Heparan sulfate proteoglycan) 


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


Functions of the basal lamina

structure, organization, filtration


Comparative size of major ECM components 


The structure of laminin

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


Model for basal lamina organization


Function: filtration

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


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 


Basal lamina at the neuromuscular junction



• 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 


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



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


Integrin link to the actin cytoskeleton 



Integrin links to intermediate filaments 


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. 


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


Defects in integrins result in:

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


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 


____ regulates the number and stability of focal adhesions 

Focal Adhesion Kinase (FAK)


Where is the extracellular matrix in this picture?

blue part


Primary ECM components 

• Polysaccharide chains 

– Glycosaminoglycans (GAGs) 

– Proteoglycans 

• Fibrous proteins 

– Collagen 

– Elastin 

– Fibronectin 

– laminin 


Fibroblasts in connective tissue are mainly made up of: 

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


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 


Four main groups of GAGs

– Hyaluronan 

– Dermatan sulfate and chondroitin sulfate 

– Heparan sulfate 

– Keratan sulfate 


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%


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 



• Also called hyaluronic acid or hyaluronate

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

• Important lubricant in joints 



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