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The Planar Polarity Protein Scribble1 Is Essential for Neuronal Plasticity and Brain Function

Lookup NU author(s): Dr Claudia Racca

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Abstract

Scribble (Scrib) is a key regulator of apicobasal polarity, presynaptic architecture, and short-term synaptic plasticity in Drosophila. In mammals, its homolog Scrib1 has been implicated in cancer, neural tube closure, and planar cell polarity (PCP), but its specific role in the developing and adult nervous system is unclear. Here, we used the circletail mutant, a mouse model for PCP defects, to show that Scrib1 is located in spines where it influences actin cytoskeleton and spine morphing. In the hippocampus of these mutants, we observed an increased synapse pruning associated with an increased number of enlarged spines and postsynaptic density, and a decreased number of perforated synapses. This phenotype was associated with a mislocalization of the signaling pathway downstream of Scrib1, leading to an overall activation of Rac1 and defects in actin dynamic reorganization. Finally, Scrib1-deficient mice exhibit enhanced learning and memory abilities and impaired social behavior, two features relevant to autistic spectrum disorders. Our data identify Scrib1 as a crucial regulator of brain development and spine morphology, and suggest that Scrib1(crc/+) mice might be a model for studying synaptic dysfunction and human psychiatric disorders.


Publication metadata

Author(s): Moreau MM, Piguel N, Papouin T, Koehl M, Durand CM, Rubio ME, Loll F, Richard EM, Mazzocco C, Racca C, Oliet SHR, Abrous DN, Montcouquiol M, Sans N

Publication type: Article

Publication status: Published

Journal: Journal of Neuroscience

Year: 2010

Volume: 30

Issue: 29

Pages: 9738-9752

Print publication date: 01/07/2010

ISSN (print): 0270-6474

ISSN (electronic): 1529-2401

Publisher: Society for Neuroscience

URL: http://dx.doi.org/10.1523/JNEUROSCI.6007-09.2010

DOI: 10.1523/JNEUROSCI.6007-09.2010


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