S-SCAM is essential for synapse formation.

Autor:	Wittenmayer N; Institute of Anatomy and Embryology, University Medical Center Göttingen, Göttingen, Germany.; Institute for Translational Medicine, MSH Medical School Hamburg, Hamburg, Germany., Petkova-Tuffy A; Institute of Anatomy and Embryology, University Medical Center Göttingen, Göttingen, Germany., Borgmeyer M; Institute for Translational Medicine, MSH Medical School Hamburg, Hamburg, Germany., Lee C; Department of Molecular Neurobiology, Synaptic Physiology Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Becker J; Institute of Anatomy and Cell Biology, University Medical Center Göttingen, Göttingen, Germany., Böning A; Institute of Anatomy and Embryology, University Medical Center Göttingen, Göttingen, Germany., Kügler S; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany., Rhee J; Department of Molecular Neurobiology, Synaptic Physiology Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Viotti JS; Institute of Anatomy and Embryology, University Medical Center Göttingen, Göttingen, Germany.; University of Bordeaux, CNRS, IINS, UMR 5297, Bordeaux, France., Dresbach T; Institute of Anatomy and Embryology, University Medical Center Göttingen, Göttingen, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular neuroscience [Front Cell Neurosci] 2023 Nov 16; Vol. 17, pp. 1182493. Date of Electronic Publication: 2023 Nov 16 (Print Publication: 2023).
DOI:	10.3389/fncel.2023.1182493
Abstrakt:	Synapse formation is critical for the wiring of neural circuits in the developing brain. The synaptic scaffolding protein S-SCAM/MAGI-2 has important roles in the assembly of signaling complexes at post-synaptic densities. However, the role of S-SCAM in establishing the entire synapse is not known. Here, we report significant effects of RNAi-induced S-SCAM knockdown on the number of synapses in early stages of network development in vitro . In vivo knockdown during the first three postnatal weeks reduced the number of dendritic spines in the rat brain neocortex. Knockdown of S-SCAM in cultured hippocampal neurons severely reduced the clustering of both pre- and post-synaptic components. This included synaptic vesicle proteins, pre- and post-synaptic scaffolding proteins, and cell adhesion molecules, suggesting that entire synapses fail to form. Correspondingly, functional and morphological characteristics of developing neurons were affected by reducing S-SCAM protein levels; neurons displayed severely impaired synaptic transmission and reduced dendritic arborization. A next-generation sequencing approach showed normal expression of housekeeping genes but changes in expression levels in 39 synaptic signaling molecules in cultured neurons. These results indicate that S-SCAM mediates the recruitment of all key classes of synaptic molecules during synapse assembly and is critical for the development of neural circuits in the developing brain. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Wittenmayer, Petkova-Tuffy, Borgmeyer, Lee, Becker, Böning, Kügler, Rhee, Viotti and Dresbach.)
Databáze:	MEDLINE
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