Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer
| Autor: | Jeffrey N. Savas, Vasily Rybakin, Nuno Apóstolo, Joris de Wit, Natalia V. Gounko, Samuel N. Smukowski, Jolijn ten Bos, Laura Trobiani, Davide Comoletti, Giuseppe Condomitti, Jeroen Vanderlinden, Sybren Portegies, Keimpe D. Wierda, Kristel M. Vennekens |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proteomics Patch-Clamp Techniques Regulator General Physics and Astronomy Hippocampal formation Interactome Synapse Mice 0302 clinical medicine lcsh:Science Cells Cultured Hippocampal mossy fiber Uncategorized Mice Knockout 0303 health sciences Multidisciplinary Pyramidal Cells CA3 Region Hippocampal medicine.anatomical_structure Mossy Fibers Hippocampal Excitatory postsynaptic potential Filopodia Mossy fiber (hippocampus) Science Primary Cell Culture Biology Inhibitory postsynaptic potential Molecular neuroscience Neural circuits General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Excitatory synapse Biological neural network medicine Animals Humans 030304 developmental biology Excitatory Postsynaptic Potentials Membrane Proteins Development of the nervous system General Chemistry Synaptic development Cellular neuroscience Rats 030104 developmental biology HEK293 Cells nervous system lcsh:Q Neuron Carrier Proteins Neuroscience 030217 neurology & neurosurgery Synaptosomes |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-21 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Excitatory and inhibitory neurons are connected into microcircuits that generate circuit output. Central in the hippocampal CA3 microcircuit is the mossy fiber (MF) synapse, which provides powerful direct excitatory input and indirect feedforward inhibition to CA3 pyramidal neurons. Here, we dissect its cell-surface protein (CSP) composition to discover novel regulators of MF synaptic connectivity. Proteomic profiling of isolated MF synaptosomes uncovers a rich CSP composition, including many CSPs without synaptic function and several that are uncharacterized. Cell-surface interactome screening identifies IgSF8 as a neuronal receptor enriched in the MF pathway. Presynaptic Igsf8 deletion impairs MF synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition. Consequently, IgSF8 loss impairs excitation/inhibition balance and increases excitability of CA3 pyramidal neurons. Our results provide insight into the CSP landscape and interactome of a specific excitatory synapse and reveal IgSF8 as a critical regulator of CA3 microcircuit connectivity and function. Mossy fiber synapses are key in CA3 microcircuit function. Here, the authors profile the mossy fiber synapse proteome and cell-surface interactome. They uncover a diverse repertoire of cell-surface proteins and identify the receptor IgSF8 as a regulator of CA3 microcircuit connectivity and function. |
| Databáze: | OpenAIRE |
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