Extracellular Matrix & Cell Adhesion Flashcards
Connexins form what junctions?
Gap junctions
What proteins play an important role in leukocyte rolling and adhesion?
Selectins, integrins, immunoglobulin family
Describe the process of leukocyte rolling & adhesion.
L-selectin on leukocytes recognizes oligosaccharides expressed on endothelial cells. E- and P-selectins on endothelial cells become activated by inflammation and recognize oligosaccharides on the leukocyte. Binding slows the leukocyte until integrins on the leukocyte are activated by chemokines. The integrins bind ICAM-1 & VCAM-1
Integrins on the leukocyte become activated by cytokines, bind to the immunoglobulin superfamily, and are brought into the cell.
What is the cause and symptoms of Marfan Syndrome?
Mutation of fibrillin gene
Defective elastin, increased TGF signaling, skeletal and vascular issues
What protein mediates cell-cell adhesion in the blood?
Selectins
Describe the structure of the basal lamina.
Highly cross-linked network of laminin, type IV collagen, and other proteins and proteoglycans.
This ECM macromolecule is composed of unbranched polysaccharide chains, is highly negatively charged, occupies a large volume, and sucks in water by attracting cations.
Glycosaminoglycans (GAGs)
Describe the process of platelet activation.
P-selectin is stored in granules in platelets. It becomes exposed through membrane flipping during platelet activation to promote aggregation.
What causes scurvy?
Vitamin C deficiency - required for hydroxylase enzymes in collagen synthesis
What are the primary functions of the extracellular matrix (ECM)?
- Adhesive substrate
- Provide structure
- Present growth factors
- Sequester & store growth factors
- Sense and transduce mechanical signals
What proteases are important in degradation of the ECM and require Ca2+ or Zn2+ for activation?
Matrix metalloproteinases (MMPs)
Focal adhesions and hemidesmosomes serve what function? How do the structures differ?
Focal adhesions and hemidesmosomes are both anchoring junctions that link the cytoskeletons of epithelial cells to the ECM.
Focal adhesions - actin linked
Hemidesmosomes - anchor intermediate filaments to ECM
What cell secretes macromolecules in most connective tissues (except bone & cartilage)?
Fibroblasts
A mutation in type I collagen may cause what disorder?
Osteogenesis imperfecta
This glycoprotein is a dimer or two subunits joined by a disulfide bond. The glycoprotein has multiple isoforms due to alternative splicing and binds collagen, proteoglycans, and integrins.
Fibronectin
Mutations in type IV collagen cause what disease and symptoms?
Alport Syndrome
Kidney disease, hearing loss, eye abnormalities
Describe the assembly of fibronectin fibrils.
Fibronectin can only assemble on cells displaying fibronectin-binding proteins (integrins). Binding to integrin links fibronectin to the actin cytoskeleton within the cell. When attached to another surface, tension from actin stretches the fibronectin and exposes cryptic binding sites that recruit more fibronectin molecules.
Fibronectin fibril assembly requires tension / mechanical need.
This fiber gives skin, blood vessels, and lungs strength and elasticity.
Elastin
What adhesion protein is necessary to form focal adhesions and hemidesmosomes that link cells to the ECM?
Integrins
Describe the formation of elastin.
Tropoelastin is secreted into the ECM, assembled, and then cross-linked with one another to form a network of elastin fibers. Microfibrils, including fibrillin, cover the elastin core and guide deposition.
This anchoring protein is homophilic and requires Ca2+. What is the protein? What junctions does this protein form?
Cadherin
Adherens junctions & desmosomes
