Biologically active sequence (KDI) mediates the neurite outgrowth functionof the gamma-1 chain of laminin-1

A neurite outgrowth domain of the gamma1-chain of laminin-1 (RDIAEIIKDI) pr omotes axon guidance of rat hippocampal neurons, regulates the nuclear move ment phase of neuronal migration, and binds to the cellular prion protein ( Liesi et al. [1995] J. Neurosci. Res. 134:447-486; Matsuzawa et al. [1998] J. Neurosci. Res. 53:114-124; Graner et al. [2000] Brain Res. Mol. Brain Re s. 76:85-92). Using electrophysiology and neuronal culture experiments, we show that this 10 amino acid peptide or its smaller domains induces potassi um currents in primary central neurons. Both these currents and the neuroto xicity of high concentrations of the 10 amino acid peptide antigen are prev ented by pertussis toxin. The smallest peptide domain capable of inducing b oth potassium currents and promoting neurite outgrowth of human spinal cord neurons is a tri-peptide KDI. Our results indicate that KDI may be the bio logically active domain of the gamma1 laminin, capable of modulating electr ical activity and survival of central neurons via a G-protein coupled mecha nism. These results expand the wide variety of functions already reported f or the members of the laminin-gene family. They suggest that biologically a ctive peptide domains of the gamma1 laminin may provide tools to promote ne uronal regeneration after injuries and to enhance neuronal survival during aging and neuronal degeneration. (C) 2001 Wiley-Liss, Inc.