title: Role for Reelin in neurotransmitter release.
abstract: The extracellular matrix molecule Reelin is known to control neuronal migration during development. Recent evidence suggests that it also plays a role in the maturation of postsynaptic dendrites and spines as well as in synaptic plasticity. Here, we aimed to address the question whether Reelin plays a role in presynaptic structural organization and function. Quantitative electron microscopic analysis of the number of presynaptic boutons in the stratum radiatum of hippocampal region CA1 did not reveal differences between wild-type animals and Reelin-deficient reeler mutant mice. However, additional detailed analysis showed that the number of presynaptic vesicles was significantly increased in CA1 synapses of reeler mutants. To test the hypothesis that vesicle fusion is altered in reeler, we studied proteins known to control transmitter release. SNAP25, a protein of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, was found to be significantly reduced in reeler mutants, whereas other SNARE complex proteins remained unaltered. Addition of recombinant Reelin to organotypic slice cultures of reeler hippocampi substantially rescued not only SNAP25 protein expression levels but also the number of vesicles per bouton area indicating a role for Reelin in presynaptic functions. Next, we analyzed paired-pulse facilitation, a presynaptic mechanism associated with transmitter release, and observed a significant decrease at CA1 synapses of reeler mutants when compared with wild-type animals. Together, these novel findings suggest a role for Reelin in modulating presynaptic release mechanisms.
authors.affiliation: Institut für Anatomie und Zellbiologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hellwig
authors.forename: Iris
authors.initials: I
authors.lastname: Hack
authors.forename: Janina
authors.initials: J
authors.lastname: Kowalski
authors.forename: Bianka
authors.initials: B
authors.lastname: Brunne
authors.forename: Joel
authors.initials: J
authors.lastname: Jarowyj
authors.forename: Andreas
authors.initials: A
authors.lastname: Unger
authors.forename: Hans H
authors.initials: HH
authors.lastname: Bock
authors.forename: Dirk
authors.initials: D
authors.lastname: Junghans
authors.forename: Michael
authors.initials: M
authors.lastname: Frotscher
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D002461:Cell Line, Transformed; D002966:Clathrin / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D055032:Electron Microscope Tomography / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D019012:Integrin beta1 / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D050683:R-SNARE Proteins / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000172:deficiency / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D000906:Antibodies; D015816:Cell Adhesion Molecules, Neuronal; D002966:Clathrin; D017077:Culture Media, Conditioned; C103773:Dab1 protein, mouse; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050683:R-SNARE Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; D049452:Green Fluorescent Proteins; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases