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Article

Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway

1
Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33077 Bordeaux, France
2
Univ. Bordeaux, CNRS, Aquitaine Institute for Cognitive and Integrative Neurosciences, UMR5287, 33405 Bordeaux, France
3
Univ. Bordeaux, CNRS, Centre de Résonance Magnétique des Systèmes Biologiques UMR5536, 33077 Bordeaux, France
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Arpad Dobolyi
Cells 2022, 11(10), 1601; https://doi.org/10.3390/cells11101601
Received: 7 April 2022 / Revised: 6 May 2022 / Accepted: 6 May 2022 / Published: 10 May 2022
(This article belongs to the Section Cell Signaling)
Social behavior is a basic domain affected by several neurodevelopmental disorders, including ASD and a heterogeneous set of neuropsychiatric disorders. The SCRIB gene that codes for the polarity protein SCRIBBLE has been identified as a risk gene for spina bifida, the most common type of neural tube defect, found at high frequencies in autistic patients, as well as other congenital anomalies. The deletions and mutations of the 8q24.3 region encompassing SCRIB are also associated with multisyndromic and rare disorders. Nonetheless, the potential link between SCRIB and relevant social phenotypes has not been fully investigated. Hence, we show that Scribcrc/+ mice, carrying a mutated version of Scrib, displayed reduced social motivation behavior and social habituation, while other behavioral domains were unaltered. Social deficits were associated with the upregulation of ERK phosphorylation, together with increased c-Fos activity. Importantly, the social alterations were rescued by both direct and indirect pERK inhibition. These results support a link between polarity genes, social behaviors and hippocampal functionality and suggest a role for SCRIB in the etiopathology of neurodevelopmental disorders. Furthermore, our data demonstrate the crucial role of the MAPK/ERK signaling pathway in underlying social motivation behavior, thus supporting its relevance as a therapeutic target. View Full-Text
Keywords: scribble; social motivation behavior; ERK/Mnk1 scribble; social motivation behavior; ERK/Mnk1
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MDPI and ACS Style

Moreau, M.M.; Pietropaolo, S.; Ezan, J.; Robert, B.J.A.; Miraux, S.; Maître, M.; Cho, Y.; Crusio, W.E.; Montcouquiol, M.; Sans, N. Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway. Cells 2022, 11, 1601. https://doi.org/10.3390/cells11101601

AMA Style

Moreau MM, Pietropaolo S, Ezan J, Robert BJA, Miraux S, Maître M, Cho Y, Crusio WE, Montcouquiol M, Sans N. Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway. Cells. 2022; 11(10):1601. https://doi.org/10.3390/cells11101601

Chicago/Turabian Style

Moreau, Maïté M., Susanna Pietropaolo, Jérôme Ezan, Benjamin J. A. Robert, Sylvain Miraux, Marlène Maître, Yoon Cho, Wim E. Crusio, Mireille Montcouquiol, and Nathalie Sans. 2022. "Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway" Cells 11, no. 10: 1601. https://doi.org/10.3390/cells11101601

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