Role for Reelin in neurotransmitter release.
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Role for Reelin in neurotransmitter release. / Hellwig, Sabine; Hack, Iris; Kowalski, Janina; Brunne, Bianka; Jarowyj, Joel; Unger, Andreas; Bock, Hans H; Junghans, Dirk; Frotscher, Michael.
In: J NEUROSCI, Vol. 31, No. 7, 7, 2011, p. 2352-2360.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Role for Reelin in neurotransmitter release.
AU - Hellwig, Sabine
AU - Hack, Iris
AU - Kowalski, Janina
AU - Brunne, Bianka
AU - Jarowyj, Joel
AU - Unger, Andreas
AU - Bock, Hans H
AU - Junghans, Dirk
AU - Frotscher, Michael
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Animals, Newborn
KW - Patch-Clamp Techniques
KW - Mutation/genetics
KW - Enzyme Inhibitors/pharmacology
KW - Antibodies/pharmacology
KW - Cell Line, Transformed
KW - Transfection/methods
KW - Green Fluorescent Proteins/genetics
KW - Action Potentials/drug effects/genetics
KW - Antigens, CD29/metabolism
KW - CA1 Region, Hippocampal/cytology
KW - Cell Adhesion Molecules, Neuronal/deficiency/immunology/pharmacology/physiology
KW - Clathrin/metabolism
KW - Culture Media, Conditioned/pharmacology
KW - Electron Microscope Tomography/methods
KW - Excitatory Postsynaptic Potentials/drug effects/genetics
KW - Extracellular Matrix Proteins/deficiency/immunology/pharmacology/physiology
KW - Gene Expression Regulation/drug effects/genetics
KW - LDL-Receptor Related Proteins/genetics
KW - Nerve Tissue Proteins/deficiency/genetics/immunology/metabolism/pharmacology/physiology
KW - Neurotransmitter Agents/metabolism
KW - Presynaptic Terminals/metabolism/ultrastructure
KW - R-SNARE Proteins/metabolism
KW - Receptors, LDL/genetics
KW - Serine Endopeptidases/deficiency/immunology/pharmacology/physiology
KW - Synapses/drug effects/metabolism/ultrastructure
KW - Synaptic Vesicles/metabolism/ultrastructure
KW - Synaptosomal-Associated Protein 25/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Animals, Newborn
KW - Patch-Clamp Techniques
KW - Mutation/genetics
KW - Enzyme Inhibitors/pharmacology
KW - Antibodies/pharmacology
KW - Cell Line, Transformed
KW - Transfection/methods
KW - Green Fluorescent Proteins/genetics
KW - Action Potentials/drug effects/genetics
KW - Antigens, CD29/metabolism
KW - CA1 Region, Hippocampal/cytology
KW - Cell Adhesion Molecules, Neuronal/deficiency/immunology/pharmacology/physiology
KW - Clathrin/metabolism
KW - Culture Media, Conditioned/pharmacology
KW - Electron Microscope Tomography/methods
KW - Excitatory Postsynaptic Potentials/drug effects/genetics
KW - Extracellular Matrix Proteins/deficiency/immunology/pharmacology/physiology
KW - Gene Expression Regulation/drug effects/genetics
KW - LDL-Receptor Related Proteins/genetics
KW - Nerve Tissue Proteins/deficiency/genetics/immunology/metabolism/pharmacology/physiology
KW - Neurotransmitter Agents/metabolism
KW - Presynaptic Terminals/metabolism/ultrastructure
KW - R-SNARE Proteins/metabolism
KW - Receptors, LDL/genetics
KW - Serine Endopeptidases/deficiency/immunology/pharmacology/physiology
KW - Synapses/drug effects/metabolism/ultrastructure
KW - Synaptic Vesicles/metabolism/ultrastructure
KW - Synaptosomal-Associated Protein 25/metabolism
M3 - SCORING: Journal article
VL - 31
SP - 2352
EP - 2360
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 7
M1 - 7
ER -