Structure and biological activity of basement membrane proteins

Abstract

Collagen type IV, laminin, heparan sulfate proteoglycans, nidogen (entactin) and SPARC) represent major structural proteins of basement membranes. They are well-characterized in their domain structures, amino acid sequences and potentials for molecular interactions. Such interactions include self-assembly processes and heterotypic binding between individual constituents, as well as binding of calcium (laminin, and are likely to be used for basement membrane assembly. Laminin, collagen IV and nidogen also possess several cell-binding sites which interact with distinct cellular receptors. Some evidence exists that those interactions are involved in the control of cell behaviour. These observations have provided a more defined understanding of basement membrane function and the definition of new research goals in the future.All multicellular animals possess various extracellular matrices. They determine body shape and stability, compartmentalization of organs and several cellular activities. These matrices include ubiquitously occurring basement membranes which are 20 -200-nm-broad deposits of some specific proteins in close proximity to epithelial, muscle, fat and nerve cells. Basement membranes are found in vertebrates and invertebrates except sponges and are produced as the first matrix during embryonic development. They are considered to control cell phenotype, tissue invasion of cells and filtration of macromolecules through glomeruli [I -41. This implies a defined supramolecular architecture for basement membranes and a distinct repertoire of biological activities expressed as the sum of their individual constituents. Yet, electron microscopy has so far revealed few details of basement membrane structure which, after staining, presents as two amorphous zones (the lamina lucida and the lamina densa) distinguished by different electron densities [5].Basement membranes are normally but not exclusively produced and deposited by cells which then remain in close contact with these structures. These contacts are mediated by specific cellular receptors which bind to some defined extracellular ligands [l -31. Other noncovalent molecular interactions maintain the matrix structure and covalent cross-links make basement membranes rather insoluble even in denaturing solvents. The increasing use of tumor models, such as the Engelbreth-Holm-Swarm (EHS) mouse tumor [6], which produce large amounts of soluble basement-membrane material has over the past decade allowed a comprehensive characterization of the major components. The progress in our understanding of the structure, biology and pathology of basement membranes 11-5 , 7 -101 as well as some methodological aspects [lo, 111 have been recently reviewed. The preCorrespondence to R . Timpl.

Entactin stimulates neutrophil adhesion and chemotaxis through interactions between its Arg-Gly-Asp (RGD) domain and the leukocyte response integrin.

“…Current concepts of basement membrane composition and structure have been presented in several recent reviews (37,38). Previously, two basement membrane components, laminin and type IV collagen, have been shown to display specific interactions with PMN (8,9,(11)(12)(13)(14).…”

Active peptides from the carboxyl‐terminal globular domain of laminin α2 and Drosophila α chains

“…Laminins are major components of basement membrane, :he thin extracellular matrix which underlies all epithelia md surrounds muscle, peripheral nerve, and fat cells [1][2][3]. Laminin-I consists of c~l, [31 and y1 chains, which assemble nto a triple-stranded coiled-coil structure in the long arm to "orm a cross-like structure ( Fig.…”

Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation

“…The laminin molecule is a cross-shaped heterotrimer consisting of one heavy a chain and two light chains, b and g chains (Timpl, 1989;Beck et al, 1990;Yurchenco and Schittny, 1990;Engle, 1992). To date, 16 laminin isoforms with different contributions of a1-a5, b1 -b3, g1-g3 chains have been identified (Miyazaki, 2006;Marinkovich, 2007).…”

“…The G domain is thought to be a major site of interaction with specific receptors on the cell surface, including integrins, syndecans and a-dystroglycan. The N-terminal region of the three chains contains functional domains that are mainly involved in matrix assembly (Timpl, 1989;Beck et al, 1990;Yurchenco and Schittny, 1990;Engle, 1992).…”