Interaction of apolipoprotein E with laminin increases neuronal adhesion and alters neurite morphology.

The extracellular matrix protein laminin profoundly affects neuronal adhesion, spreading, differentiation, and growth by binding integrin-type cell surface receptors. Laminin binds other basement membrane components, including heparan sulfate proteoglycans. Apolipoprotein E (apoE) also binds basement membrane and heparan sulfate proteoglycans and colocalizes with s-laminin in the neuromuscular junction. We sought to determine whether apoE interacts with laminin and whether, as a result, apoE alters the regulation of neuronal adhesion and differentiation by laminin. We demonstrate high-avidity interaction between apoE and laminin in vitro. Compared to laminin alone, a laminin-apoE substrate produces increased numbers of live, attached hippocampal neurons in culture. In addition, neurons grown on laminin-apoE substrates have larger growth cones, increased neuritic branching, and flattened cell bodies compared to neurons grown on laminin alone. ApoE may be important in the development and maintenance of neurons in the central nervous system by regulating interactions between the neuron and the extracellular matrix.