I give this lecture in the Cell Biology and Genetics course for first-year veterinary students. The core material comes from Alberts' Molecular Biology of the Cell, Fifth Edition. I have added multiple clinical examples, both human and veterinary.
Unblocking The Main Thread Solving ANRs and Frozen Frames
Extracellular Matrix lecture
1. Extracellular Matrix
Antonia Jameson Jordan, D.V.M., Ph.D.
November 21, 2008
Outline:
• Overview of structural and
signaling roles of ECM
• Two main classes of ECM
molecules
– Glycosaminoglycan
polysaccharide chains
• Structure and function
– Fibrous proteins
• Structure and function
• Basal lamina (basement
membrane)
• Integrins
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5. Role of HA in morphogenesis:
• Acts as space filler and facilitator of cell
migration
– If synthesized on the basal side of an
epithelium, creates a cell-free space into
which other cells can migrate
The role of HA in atrioventricular canal
morphogenesis:
Itano, N. J Biochem 2008 144:131-137; doi:10.1093/jb/mvn046
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8. Skin turgor test to assess hydration status:
Blowey & Weaver, Diseases and Disorders of Cattle (Mosby, 1997)
Signaling roles of proteoglycans:
• Proteoglycans can regulate the activities of
secreted proteins
– Gels formed by GAG chains act as “sieves” that
regulate passage of molecules by size and charge
– Bind secreted signaling molecules
• Control diffusion, range of action, lifetime, modify signaling
activity
– e.g.,heparan sulfate immobilizes chemokines on the endothelial
surface of a blood vessel at a site of inflammation
• Cell-surface proteoglycans act as co-receptors
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12. Collagen type IV forms a fine meshwork:
• More flexible structure
than fibrillar collagens
• Interruptions of triple-
helical structure
• Not cleaved after
secretion
• Interact via uncleaved
terminal domains to
assemble into a flexible
network
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Type 1 collagen diseases
(Osteogenesis imperfecta):
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November 2008 05:31 PM)
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13. Type 1 collagen diseases
(Osteogenesis imperfecta):
Clinical signs and diagnosis of osteogenesis
imperfecta in three dogs (Ron Minor et al,1997)
Seeliger et al: Osteogenesis imperfecta in two litters of Dachsunds. Vet Pathol 40: 530-539, 2003
Ehlers-Danlos syndrome:
• Defect in synthesis or structure of fibrillar collagen (mutations have
been found in collagen types I, III, V)
– Skin hyperextensibility, joint laxity, fragile skin and vessels, poor
wound healing
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18. Basal laminae have diverse functions:
• Structural
– Critical role in the architecture of an organ
– Mechanical connection between epithelia and
underlying connective tissue
• Scaffold for tissue regeneration
Basal laminae have diverse functions:
• Selective filtration
– Glomerulus
• Selective barrier to cell movement
• Spatial organization of the components of the
neuromuscular junction
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