I love TG2 ® Cytoskeleton- ECM and cell junctions ECM- extracellular matrix Extracellular Matrix (ECM): the non-cellular extracellular component present within all tissues and organs. ECM provides not only an essential physical scaffolding for the cellular constituents, but also initiates crucial biochemical and biomechanical cues that are required for tissue morphogenesis, differentiation and homeostasis. Characteristics of ECM: . The classes of the ECM macromolecules in the ECM in different animal tissues are broadly similar. However, variations in the relative amounts of these macromolecules and in the ways in which they are organized differ . The ECM exists in different forms and texture depending on the location and function Components of ECM: · Glycosaminoglycans (GAGs): large and highly charged, usually covalently linked to protein in the form of proteoglycans (~36) · Fibrous proteins: primarily members of the collagen family (~40) · Non-collagen glycoproteins: carrying conventional asparagine-linked oligosaccharides, e.g. Fibronectin · Other matrix-associated proteins that can modify matrix behaviour by crosslinking, degradation or other mechanisms Extracellular matrix- collagens Collagens: · A family of fibrous proteins secreted in large quantities by connective-tissue cells · Major component of skin (dermis) and bone · Most abundant protein in mammals · Extremely rich in proline and glycine · (fibroblasts are the main ones) Types of Collagen (In humans 19 types identified in the body) · Fibril-forming (Fibrillar): > Type I: Bone, skin, tendons, ligaments etc. (accounts for 90% of body collagen) > Type II: Cartilage, intervertegral disc etc. > Type III: Skin, blood vessels, internal organs etc. Type V: Dermis, bone tendon etc. · Fibril-associated: · Network-forming: Sheet-like network and anchoring fibrils, e.g. Collagen IV · Transmembrane: Non-fibrillar, e.g. Collagen XIII · Proteoglycan core protein: Non-fibrillar > Cellular functions: · Supporting cell adhesion, migration and differentiation · Regulating cell signalling · Entrapping growth factors and cytokines > Physiological functions: · Imparting support, strength, shape and elasticity to the tissues · Providing flexibility, support and movement to cartilage · Protecting delicate organs, such as kidneys and spleen · Wound healing > Pathological conditions: · Genetic disorders · Ageing ECM - elastin Elastin: · Highly hydrophobic protein · Rich in proline and glycine · Not glycosylated (post translational modification) · Secreted as tropoelastin (biosynthetic precursor of elastin) · Following secretion, tropoelastin molecules become crosslinked to one another to generate an extensive network of elastin fibers and sheets · The dominant extracellular matrix protein in arteries giving elasticity ECM- non-collagen glycoproteins Fibronectin (FN)
I love TG2 ® · A dimer composed of two very large subunits (MW 220,000) joined by disulfide bonds at their C-terminal ends. · The Arg-Gly-Asp (RGD) sequence is important in regulating cell-ECM adhesion via interaction with integrins · FN is important in fibrillar adhesions · Has many binding sites for other intracellular matrix proteins to bind to. · Promoting cell survival, proliferation, and differentiation · Serving as highways for cell migration Cell adhesion 1 Cell adhesion is the binding of a cell to a surface or substrate, such as an extracellular matrix or to another