A motoneuron-selective stop signal in the synaptic protein S-laminin.
Motor axons preferentially reinnervate original synaptic sites on denervated muscle fibers. We have shown that components of synaptic basal lamina direct this selectivity, and we identified a protein, s-laminin, that is concentrated in synaptic basal lamina. Here, we report that a recombinant s-laminin fragment inhibits neurite outgrowth promoted by laminin. A tripeptide sequence in this fragment, Leu-Arg-Glu (LRE), contributes to this inhibition and is itself sufficient to inhibit outgrowth. LRE-mediated inhibition is selective for motoneuron-like cells and is observed in mixtures with several, but not all, outgrowth-promoting substrates. Growth cones extending on laminin stop for up to several hours upon contacting deposits of the s-laminin fragment. Thus, LRE may serve as a cell type-selective and context-dependent target-derived signal that plays a role in synapse formation.
Porter
B E
BE
Department of Anatomy and Neurobiology Washington University School of Medicine St. Louis, Missouri 63110.
Weis
J
J
Sanes
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000502:physiology; D007797:Laminin / Q000096:biosynthesis / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
D007797:Laminin; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C058783:laminin beta2