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  Genetic evidence for the adhesion protein IgSF9/Dasm1 to regulate inhibitory synapse development independent of its intracellular domain

Mishra, A., Traut, M. H., Becker, L., Klopstock, T., Stein, V., & Klein, R. (2014). Genetic evidence for the adhesion protein IgSF9/Dasm1 to regulate inhibitory synapse development independent of its intracellular domain. The Journal of Neuroscience, 34(12), 4187-4199. doi:10.1523/JNEUROSCI.3671-13.2014.

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 Creators:
Mishra, Archana1, Author           
Traut, Matthias H.1, 2, Author           
Becker, Lore, Author
Klopstock, Thomas, Author
Stein, Valentin2, Author           
Klein, Rüdiger1, Author           
Affiliations:
1Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society, ou_1113546              
2Max Planck Research Group: Synaptic Receptor Trafficking / Stein, MPI of Neurobiology, Max Planck Society, ou_1113557              

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Free keywords: CELL-ADHESION; DENDRITE ARBORIZATION; SEIZURE SUSCEPTIBILITY; MATURATION-1 DASM1; IG SUPERFAMILY; FAMILY-MEMBER; NEUROLIGIN 2; IN-VIVO; TURTLE; DIFFERENTIATION
 Abstract: Normal brain function requires balanced development of excitatory and inhibitory synapses. An imbalance in synaptic transmission underlies many brain disorders such as epilepsy, schizophrenia, and autism. Compared with excitatory synapses, relatively little is known about the molecular control of inhibitory synapse development. We used a genetic approach in mice to identify the Ig superfamily member IgSF9/Dasm1 as a candidate homophilic synaptic adhesion protein that regulates inhibitory synapse development. IgSF9 is expressed in pyramidal cells and subsets of interneurons in the CA1 region of hippocampus. Electrophysiological recordings of acute hippocampal slices revealed that genetic inactivation of the IgSF9 gene resulted in fewer functional inhibitory synapses; however, the strength of the remaining synapses was unaltered. These physiological abnormalities were correlated with decreased expression of inhibitory synapse markers in IgSF9(-/-) mice, providing anatomical evidence for a reduction in inhibitory synapse numbers, whereas excitatory synapse development was normal. Surprisingly, knock-in mice expressing a mutant isoform of IgSF9 lacking the entire cytoplasmic domain (IgSF9(Delta C/Delta C) mice) had no defects in inhibitory synapse development, providing genetic evidence that IgSF9 regulates synapse development via ectodomain interactions rather than acting itself as a signaling receptor. Further, we found that IgSF9 mediated homotypic binding and cell aggregation, but failed to induce synapse formation, suggesting that IgSF9 acts as a cell adhesion molecule (CAM) to maintain synapses. Juvenile IgSF9(-/-) mice exhibited increased seizure susceptibility indicative of an imbalance in synaptic excitation and inhibition. These results provide genetic evidence for a specific role of IgSF9 in inhibitory synapse development/maintenance, presumably by its CAM-like activity.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Issued
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: The Journal of Neuroscience
  Other : The Journal of Neuroscience: the Official Journal of the Society for Neuroscience
  Abbreviation : J. Neurosci.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, DC : Society of Neuroscience
Pages: - Volume / Issue: 34 (12) Sequence Number: - Start / End Page: 4187 - 4199 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187_1