Basement Membranes: Cell Scaffoldings and Signaling Platforms

Basement membranes are widely distributed extracellular matrices that coat the basal aspect of epithelial and endothelial cells and surround muscle, fat, and Schwann cells. These extracellular matrices, first expressed in early embryogenesis, are self-assembled on competent cell surfaces through binding interactions among laminins, type IV collagens, nidogens, and proteoglycans. They form stabilizing extensions of the plasma membrane that provide cell adhesion and that act as solid-phase agonists. Basement membranes play a role in tissue and organ morphogenesis and help maintain function in the adult. Mutations adversely affecting expression of the different structural components are associated with developmental arrest at different stages as well as postnatal diseases of muscle, nerve, brain, eye, skin, vasculature, and kidney.The basement membrane (basal lamina) was first described in muscle as a “membranaceous sheath of the most exquisite delicacy” (Bowman 1840). Microscopists subsequently identified basement membranes in nearly all tissues. In the late 1970s, the discovery of the basement membrane-rich EHS tumor led to the isolation of abundant quantities of laminin, type IV collagen, nidogen (entactin), and perlecan, enabling elucidation of their biochemical and cell-interactive properties and opening a door to an understanding of structure and function of basement membranes at a molecular level.Basement membranes are layered cell-adherent extracellular matrices (ECMs) that form part of tissue architecture, contributing both to embryonic differentiation and the maintenance of adult functions. They are evolutionarily ancient structures, likely appearing when organized communities of animal cells first emerged. These matrices serve as an extension of the plasma membrane, protecting tissues from disruptive physical stresses, and provide an interactive interface between cell and surrounding environment that can mediate local and distant signals within and between these compartments. Such signals appear to be largely processed through integrins, growth factor interactions, and dystroglycan. Basement membrane-dependent functions include the promotion of strong epidermal/dermal attachment, stabilization of the skeletal muscle sarcolemma, selectivity of glomerular filtration, and establishment of epithelial and glial cell polarization. Assembly of a functionally active basement membrane depends on the binding interactions among the large carbohydrate-modified proteins, each consisting of an array of distinct domains with unique binding properties. These components, in turn, are organized into higher ordered supramolecular assemblies that engage cell surface receptors in a developmentally and tissue-specific manner. In this review models of structure will be related to those of function based on a consideration of morphological, biochemical, cell biological, developmental, and genetic information.