A Modular Organization of LRR Protein-Mediated Synaptic Adhesion Defines Synapse Identity

Pyramidal neurons express rich repertoires of leucine-rich repeat (LRR)-containing adhesion molecules with similar synaptogenic activity in culture. The in vivo relevance of this molecular diversity is unclear. We show that hippocampal CA1 pyramidal neurons express multiple synaptogenic LRR proteins...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2018-07, Vol.99 (2), p.329-344.e7
Main Authors: Schroeder, Anna, Vanderlinden, Jeroen, Vints, Katlijn, Ribeiro, Luís F., Vennekens, Kristel M., Gounko, Natalia V., Wierda, Keimpe D., de Wit, Joris
Format: Article
Language:English
Subjects:
Animals
Brain
CA1 pyramidal neuron
Cells, Cultured
Coculture Techniques
Excitatory Postsynaptic Potentials - physiology
Experiments
Female
Gene expression
glutamatergic transmission
Grants
HEK293 Cells
Hippocampus
Humans
Immunoglobulins
Leucine
leucine-rich repeat
Localization
Male
Mammals
Membrane Glycoproteins - analysis
Membrane Glycoproteins - physiology
Membrane Glycoproteins - ultrastructure
Membrane Proteins - analysis
Membrane Proteins - physiology
Membrane Proteins - ultrastructure
Mice
Mice, Inbred C57BL
Mice, Knockout
molecular diversity
Neural Cell Adhesion Molecules - analysis
Neural Cell Adhesion Molecules - physiology
Neural Cell Adhesion Molecules - ultrastructure
Neurons
neurotransmitter receptor
Phenotypes
Postsynaptic density
Proteins
Pyramidal cells
Rats
Rats, Wistar
Receptor density
Schaffer collateral
Structure-function relationships
Synapses - chemistry
Synapses - physiology
Synapses - ultrastructure
synaptic adhesion
synaptic specificity
Synaptic transmission
Synaptic Transmission - physiology
synaptogenesis
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
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Summary:Pyramidal neurons express rich repertoires of leucine-rich repeat (LRR)-containing adhesion molecules with similar synaptogenic activity in culture. The in vivo relevance of this molecular diversity is unclear. We show that hippocampal CA1 pyramidal neurons express multiple synaptogenic LRR proteins that differentially distribute to the major excitatory inputs on their apical dendrites. At Schaffer collateral (SC) inputs, FLRT2, LRRTM1, and Slitrk1 are postsynaptically localized and differentially regulate synaptic structure and function. FLRT2 controls spine density, whereas LRRTM1 and Slitrk1 exert opposing effects on synaptic vesicle distribution at the active zone. All LRR proteins differentially affect synaptic transmission, and their combinatorial loss results in a cumulative phenotype. At temporoammonic (TA) inputs, LRRTM1 is absent; FLRT2 similarly controls functional synapse number, whereas Slitrk1 function diverges to regulate postsynaptic AMPA receptor density. Thus, LRR proteins differentially control synaptic architecture and function and act in input-specific combinations and a context-dependent manner to specify synaptic properties. [Display omitted] •Single hippocampal CA1 neurons express multiple synaptic organizing LRR proteins•FLRT2 regulates dendritic spine density in CA1 neurons•LRRTM1 and Slitrk1 organize synaptic vesicle distribution in an opposing manner•Input-specific combinations of LRR proteins specify synaptic properties Hippocampal CA1 pyramidal neurons express multiple synaptogenic leucine-rich repeat (LRR)-containing adhesion molecules. Schroeder et al. show that LRR proteins differentially control synaptic structure and function and act in input-specific combinations and a context-dependent manner to specify synaptic properties.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2018.06.026