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2 results on '"Joris de Wit"'

1. Leucine-rich repeat-containing synaptic adhesion molecules as organizers of synaptic specificity and diversity

Author

Anna Schroeder and Joris de Wit

Subjects
Medicine, Biochemistry, QD415-436
Abstract

Brain circuits: Regulating synaptic connections Further analysis of synaptic proteins will provide insights into the functioning of neural circuits and associated brain disorders. The brain houses numerous highly specialized neuron types, which transfer and process information via a complex network of synaptic connections. Every neuron develops its own distinctive synapses with specific functions, but exactly how this is achieved is not clear. Joris de Wit and Anna Schroeder at the VIB Center for Brain and Disease Research in Leuven, Belgium, reviewed recent research into the leucine-rich repeat-containing (LRR) proteins, which are thought to be major organizers of synaptic connectivity and key regulators of healthy neural circuit development. Further investigations into the functionality of LRR proteins in the brain will not only improve understanding of neural circuitry but also provide insights into synaptic impairments in brain disorders like schizophrenia.

Published
2018
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2. Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

Author

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, and Kristel M. Vennekens

Subjects
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
Abstract

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.

Published
2020

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