Extracellular Matrix and Cell Adhesion Flashcards
- Discuss the contributions of the ECM to cell and tissue function.
- Define the four major classes of ECM components and their properties.
- Define two types of fibrillar proteins and at least two types of multidomain adapter proteins of the ECM.
- Discuss the role of MMPs in ECM remodeling.
- Discuss the role of adhesion in cell function and survival.
- Define and describe at least three different types of cell adhesion molecules (CAMs) and their ligands.
- Discuss the role of CAMs in signaling.
- Describe proteins associated intracellularly with CAMs.
- Discuss the ECM and cell adhesion in the context of disease processes.
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ECM is non-cellular excreted material
Define the four major classes of ECM components and their properties.
1) glycosaminoglycans (GAGs) [proteoglycans]
2) fibrous proteins [collagen, elsastin]
3) multidomain adapter proteins [fibronectin and laminin]
4) water and many solutes
Discuss the contributions of the ECM to cell and tissue function.
Most mammalian cell types, adhesion to other cells or the extracellular matrix (ECM) is critical for cell survival [not cancer cells]. Relative amount of ECM dependent on tissue type [connective vs neural, for example]
Cell adhesion is specific and selective [fibroblasts only grown on fibronectin].
The ECM serves not only as a scaffold for cells but also participates in regulating various cell functions (survival, differentiation, migration, proliferation, and shape).
ECM cells made by members of the fibroblast family [chondroblasts, fibroblasts, depending on tissue type]
What are two fibrillar proteins?
Collagen, elastin
What are two multidomain adapter proteins?
Fibronectin, laminin
What are MMPs?
Matrix Metalloproteases.
[extracellular proteases secreted to turn over the ECM; particularly important in tissue remodeling during development and in cell invasion of tissues]
What is the significance of cell adhesion molecules?
Cell adhesion molecules are not simply adhesive devices: For adhesion and force generation against the ECM or other cells, they form a trans-membrane link with the cytoskeleton. When bound to a ligand, CAMs signal their engagement via conformational change to the cell interior, thus affecting cell function.
Define and describe at least three different types of cell adhesion molecules (CAMs) and their ligands.
1) Cadherins [bind other cadherins = homophilic]
2) Ig Superfamily (IgSF) CAMs [homophilic]
3) Integrins [bind ECM]
Discuss the role of CAMs in signaling. Describe proteins associated intracellularly with CAMs.
In addition to providing the cytoskeletal link, CAM-associated proteins also are involved in the regulation of adhesion, in the control of actin polymerization, and in cell signaling mediated by CAMs. For example, assembly of adhesion sites requires the action of protein tyrosine kinases, whereas disassembly and detachment appears to require protein kinase C activity. Members of the Rho family of small GTPases involved in the regulation of F-actin polymerization (see Cell Motility) also are associated with certain CAMs. It follows that CAMs are paired on the cytoplasmic face of the membrane with complex protein assemblies that serve mechanical, controlling, and signaling functions. It is not surprising, therefore, that these adhesion sites play major roles in cell differentiation/development and cancer. In development, CAMs change as cells differentiate.
_____ mutations are relatively frequent. They interfere with osteogenesis and cause skeletal dysplasias.
Collagen I
_____ null mutant mice are early embryonic lethal.
Fibronectin
[Because of the severe consequences (developmental and other) loss-of-function of a CAM may result in embryonic lethality (see fibronectin, above).]
Some ______ mutations have been linked to nephrotic syndrome (glomerular filtration defect) and to neuromuscular junction/muscle innervation problems in children.
laminin
Loss-of-function mutations of ______ cause inherited osteolysis/arthritis syndromes and bone dysplasias.
matrix metalloproteases (MMP) 2 or 13
Overexpression of some MMPs, specifically (3), correlates with high invasiveness and poor prognosis in many cancers.
MMP2, MMP9 and MMP14
Two types of leukocyte adhesion deficiencies have been identified:
- Type I, affecting a particular integrin.
- Type II, affecting a selectin, a CAM involved in leukocyte rolling (the initial contact with vascular endothelial cells, prior to adhesion and extravasation).
