Adamtsl3 mediates DCC signaling to selectively promote GABAergic synapse function.

Autor:	Cramer TML; University of Zurich, Institute of Pharmacology and Toxicology, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Pinan-Lucarre B; University Claude Bernard Lyon 1, CNRS UMR 5284, INSERM U 1314, Melis, 69008 Lyon, France., Cavaccini A; University of Zurich, Brain Research Institute, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Damilou A; University of Zurich, Brain Research Institute, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Tsai YC; University of Zurich, Institute of Pharmacology and Toxicology, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Bhat MA; University of Zurich, Institute of Pharmacology and Toxicology, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Panzanelli P; Department of Neuroscience Rita Levi Montalcini, University of Turin, Turin, Italy., Rama N; Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France., Mehlen P; Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France., Benke D; University of Zurich, Institute of Pharmacology and Toxicology, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Karayannis T; University of Zurich, Brain Research Institute, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Bessereau JL; University Claude Bernard Lyon 1, CNRS UMR 5284, INSERM U 1314, Melis, 69008 Lyon, France., Tyagarajan SK; University of Zurich, Institute of Pharmacology and Toxicology, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: shiva.tyagarajan@gmail.com.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Aug 29; Vol. 42 (8), pp. 112947. Date of Electronic Publication: 2023 Aug 10.
DOI:	10.1016/j.celrep.2023.112947
Abstrakt:	The molecular code that controls synapse formation and maintenance in vivo has remained quite sparse. Here, we identify that the secreted protein Adamtsl3 functions as critical hippocampal synapse organizer acting through the transmembrane receptor DCC (deleted in colorectal cancer). Traditionally, DCC function has been associated with glutamatergic synaptogenesis and plasticity in response to Netrin-1 signaling. We demonstrate that early post-natal deletion of Adamtsl3 in neurons impairs DCC protein expression, causing reduced density of both glutamatergic and GABAergic synapses. Adult deletion of Adamtsl3 in either GABAergic or glutamatergic neurons does not interfere with DCC-Netrin-1 function at glutamatergic synapses but controls DCC signaling at GABAergic synapses. The Adamtsl3-DCC signaling unit is further essential for activity-dependent adaptations at GABAergic synapses, involving DCC phosphorylation and Src kinase activation. These findings might be particularly relevant for schizophrenia because genetic variants in Adamtsl3 and DCC have been independently linked with schizophrenia in patients. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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