ECM Proteins

3 Major ECM proteins

1. Collagen

2. Elastin

3. Fibronectin

Extracellular Matrix

Biological "glue" - three kinds of protein fibers interwoven in this matrix: collagen, elastin, fibronectin

Collagen

Cable-like fibers or sheets provide tensile strength (resists longitudinal stress)

Elastin

Rubberlike protein fiber, abundant in tissues that stretch and return to original shape (such as lungs)

Fibronectin

Promotes cell adhesion, holds cells in position

• Amount reduced in some types of cancer cells (decreased cell adhesion may promote metastasis)

HERDA (Hereditary Equine Regional Dermal Asthenia)

• Autosomal recessive connective tissue disorder

• Caused by homozygous recessive mutation that weakens collagen fibers (shortened and thinned collagen fibrils in the deep dermis)

Elastin

• Found in many tissues to resume their shape after stretching or contracting

• High quantities in highly elastic blood vessels (such as aorta), lungs, elastic ligaments and cartilage, skin, bladder

• Absence causes cutis laxa (skin hangs in folds, inelastic)

• Spontaneous microdeletion of one copy of elastin gene associated with some symptoms of Williams syndrome (elfin facial features associated with low levels elastin in this syndrome)

• If only one copy of gene is present, called hemizygous

• Destruction of elastin and collagen a major feature of emphysema

Fibronectin Domain Structure

• Collagen, fibrin, heparin and other ECM proteins can bind to fibronectin

• Since has 2 identical subunits, lots of cross-linking to EMC proteins and cells can occur

• Critical for creation of an ECM 'net' around cells; helps keep cells in place

• The RGD sequence (arginine-glycine-aspartic acid amino acid sequence) of fibronectin facilitates integrin (a CAM) binding to ECM, restricting cell migration

• RGD binding to cell integrins also can signal cell to change behavior (produce more specific compounds, grow faster, etc.)