The nature and biology of basement membranes

Abstract

Basement membranes are delicate, nanoscale and pliable sheets of extracellular matrices that often act as linings or partitions in organisms. Previously considered as passive scaffolds segregating polarized cells, such as epithelial or endothelial cells, from the underlying mesenchyme, basement membranes have now reached the center stage of biology. They play a multitude of roles from blood filtration to muscle homeostasis, from storing growth factors and cytokines to controlling angiogenesis and tumor growth, from maintaining skin integrity and neuromuscular structure to affecting adipogenesis and fibrosis. Here, we will address developmental, structural and biochemical aspects of basement membranes and discuss some of the pathogenetic mechanisms causing diseases linked to abnormal basement membranes.

Keywords: Collagen; Discoidin domain receptor; Heparan sulfate proteoglycan; Integrin; Laminin.

Fig. 1

Core Basement Membrane Components and Binding Interactions. Laminins (Lms) are central organizers of BMs. Lm111, a prototypical laminin expressed in embryogenesis, binds to cell surface sulfated glycolipids (SGL), several integrins, α-dystroglycan (αDG), nidogens (Nd), agrin, and polymerizes via its LN domains. Collagen-IV (three isoforms) and perlecan bind to nidogen, completing the core basement membrane scaffold. Agrin and perlecan HS chains attach to growth factors, promoting their interactions with receptor tyrosine kinases (RTK). Integrin and αDG attach through adaptor proteins to the cytoskeleton. Lm411, an isoform that does not polymerize, exhibits weak integrin and αDG binding but strong binding to SGLs (gal sulfatide). Lm511/521, polymerizing laminins, binds to multiple integrins both in the LG domains and α5 short arm, to the Lutheran receptor (Lu), and moderately well to αDG. Lm3A32, a non-polymerizing laminin found in epithelia, binds strongly to α6β4 integrin of hemidesmosomes and links to collagen VII of the anchoring fibrils.