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 is the most common collagen type?
Type I - skin & bone
What proteins are necessary to form tight junctions / occluding junctions? What is the purpose of each?
Claudin - forms tight seals through homophilic interactions
Occludin - limits permeability
Zona occludens - provide structural support
What proteins are important for platelet aggregation?
P-selectin & integrin
What are the functions of the anchoring junctions?
Link cytoskeletons of adjacent cells
Link cytoskeletons of epithelial cells to the extracellular matrix
What anchoring junctions link the cytoskeletons of adjacent cells? How do these junctions differ?
Adherens junctions - anchor to actin, more flexible
Desmosomes - anchor to intermediate filaments, strong and provide more structure
What is the simplest GAG?
Hyaluronic acid
What is the function of gap junctions?
Form channels linking cytoplasms of adjacent cells for passage of small water-soluble molecules
These proteins are expressed on endothelial cells and form heterophilic interactions with integrins on leukocytes.
Immunoglobulin superfamily → specifically intracellular cell adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAM)
What fibrous protein is released by fibroblasts prior to the formation of collagen fibrils to help guide their organization?
Fibronectin
How does fibronectin bind to integrins?
Via RGD (arginine-glycine-aspartate) sequence
What proteins typically compose the basal lamina?
Laminin & Type IV collagen
What is the importance of leukocyte rolling and adhesion?
The process enables leukocytes to be pulled into endothelial cells from the bloodstream to target sites of inflammation.
Describe the structure and characteristics of collagen.
Triple-helical structure of alpha chains, rich in proline and glycine, resists tensile stress
What adhesion protein is necessary to form focal adhesions and hemidesmosomes that link cells to the ECM?
Integrins
This disorder is characterized by mutations in collagen genes that cause hypermobility, stretchy skin, and/or rupture of blood vessels.
Ehlers-Danlos Syndrome
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.
What is a proteoglycan?
GAG covalently linked to a core protein
What is Goodpasture Syndrome?
Autoimmune disorder that affects the lungs and kidneys. Antibodies attack collagen in the basement membrane of the kidney and alveoli of the lungs.
What are the major macromolecules always present in the ECM?
Glycosaminoglycans (GAGs), fibrous proteins (collagen & elastin), and glycoproteins
What are the functions of the basal lamina?
Molecular filter - in the glomerulus of the kidney
Selective barrier - prohibits passage of fibroblasts, but allows other small molecules
Tissue regeneration - scaffold for migration of regenerating cells
What are the three types of selectins?
L-selectin → WBC
P-selectin → platelets & endothelial cells
E-selectin - activated endothelial cells
What are the four types of anchoring cell junctions?
Adherens junctions
Desmosomes
Focal Adhesions
Hemidesmosomes
Desmosomes are more plentiful in tissues exposed to high mechanical stress, such as the skin and heart. Why is this?
Desmosomes provide mechanical strength.
This anchoring protein is homophilic and requires Ca2+. What is the protein? What junctions does this protein form?
Cadherin
Adherens junctions & desmosomes
What is the function of hyaluronic acid?
To resist forces in tissues and joints
What junction plays a role in mechanotransduction?
Adherens junctions
This type of junction holds cells tightly together at the apex.
Tight junctions / occluding junctions
