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Laminar Basement Membranes

There is an important group of molecules outside of the cells which is called the extracellular matrix (ECM) or 'Basement Membrane.' These molecules were long ignored, much as the packing materials in a box are ignored and discarded when one removes the objects packed in the box. ECM molecules are vitally important to cells because they bind to receptor molecules on the surface of the cell and send signals that regulate which genes are active. One of the major ECM molecules is laminin, a large cross-shaped glycoprotein. The laminins are a family of extracellular matrix glycoproteins localized in the basement membrane that separates epithelial cells from the underlying somatic tissues. They are also found in basement membranes surrounding fat, muscle and peripheral nerve cells. Laminin is the extracellular glue that literally holds our tissues together and makes us one body.

Laminin Structure

The laminins are large glycoproteins comprising three different disulphide-bonded chains. Laminin nomenclature is based on which of 3-5 polypeptide chains the molecule contains. For example, Laminin-521 has the #5 alpha helix, the #2 beta helix and the #1 gamma helix comprising the three-part chain structure. The laminins are the primary extracellular matrix molecules to be observed in the developing embryo and have potent biological activities. In addition, there have been new developments in the number and localization of the homologues of the laminin chains and the role of laminin in neuromuscular disease. Their primary role is in cell-matrix attachment, but many additional biological activities, including promoting cell growth and migration, tumor growth and metastases(cancer growth), neuron outgrowth, nerve regeneration, wound repair and graft survival, have been demonstrated. Many of these biological activities are duplicated by proteolytic fragments of laminin and by small laminin-derived synthetic peptides. These laminin-derived peptides may be useful clinical reagents for accelerating wound healing with minimal scarring or for blocking tumors. Laminins are incredibly important component of our connective tissues, contained mostly in the basement membranes throughout the human body and all animals. The laminins include fifteen identified varieties of cross-shaped glycoproteins making up the extracellular matrix that connects to collagen, providing a molecular framework supporting tissues and determining how healing takes place in some organ systems such as the CNS and kidneys. According to various sources, laminin (especially laminin5) is involved in intracellular communication and even in clotting as well as healing. The expression of laminin production is controlled by growth hormone and laminins are involved in directing cells to the correct place during the body's response to injury. One of laminin's main functions is to help epithelial cells in basement membranes, including blood vessels, to communicate with other cells and to know where to move during developmental stages. Laminins play extremely important roles in the body and are allowing physicians to heal and regenerate the body's tissues.

Laminin Isomers and Binding

<nowiki>There are about 15 known different types or isomers of laminin glycoproteins that consists of one alpha, one beta, and one gamma protein chains, making a trimeric complex of strands encircling a cross shaped sugar backbone. These laminin glycoproteins are classified according to which polypeptide chains are included. For example, the laminin-5 molecule was renamed laminin-332 and laminin 10 was renamed laminin-511 that contain one of five alpha chains, one of three beta chains, and one of three possible gamma chains. These two particular laminins are critical to the structure of the laminar basement membrane of skin tissue between the epidermal dermal layers. The portion of the laminin molecule that binds laminar membrane together is the globular LG domain at the bottom of the cross. The LG domain is the C-terminal portion of the alpha helix with five different defined subdomains. Since the variety of five possible alpha helices varies the shade of the LG domain, C-terminal ends very among the laminins. There are also a variety of membrane receptors that bind LG domain of laminins: syndacans, a-dystroglycan, and integrins. On the top of the cross shaped laminin molecule is the N-terminal domain which is important for the binding of laminin together with other matrix molecules. Although laminin-332 undergoes proteolytic activation after secretion, laminin-511 is secreted in active form and incorporated immediately in the membrane between the epidermis and the dermis layer throughout the integumentary system (Sugawara, et al, 2008).