Biologically active sequence (KDI) mediates the neurite outgrowth function of the gamma-1 chain of laminin-1.
A neurite outgrowth domain of the gamma1-chain of laminin-1 (RDIAEIIKDI) promotes axon guidance of rat hippocampal neurons, regulates the nuclear movement 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 Res. 76:85-92). Using electrophysiology and neuronal culture experiments, we show that this 10 amino acid peptide or its smaller domains induces potassium currents in primary central neurons. Both these currents and the neurotoxicity of high concentrations of the 10 amino acid peptide antigen are prevented by pertussis toxin. The smallest peptide domain capable of inducing both potassium currents and promoting neurite outgrowth of human spinal cord neurons is a tri-peptide KDI. Our results indicate that KDI may be the biologically active domain of the gamma1 laminin, capable of modulating electrical activity and survival of central neurons via a G-protein coupled mechanism. These results expand the wide variety of functions already reported for the members of the laminin-gene family. They suggest that biologically active peptide domains of the gamma1 laminin may provide tools to promote neuronal regeneration after injuries and to enhance neuronal survival during aging and neuronal degeneration.
Liesi
P
P
The Brain Laboratory, Biomedicum Helsinki, Institute of Biomedicine (Anatomy), University of Helsinki, PO Box 63 (Haartmaninkatu 8), 00014 Helsinki, Finland. paivi.liesi@helsinki.fi
Laatikainen
T
T
Wright
J M
JM
D000595:Amino Acid Sequence / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007797:Laminin / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D037342:Pertussis Toxin; D011247:Pregnancy; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007473:Ion Channels; D007797:Laminin; D009414:Nerve Growth Factors; D009498:Neurotoxins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; C121346:laminin 1; C089141:laminin gamma 1; D037342:Pertussis Toxin