Journal
JOURNAL OF NEUROSCIENCE
Volume 30, Issue 29, Pages 9738-9752Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.6007-09.2010
Keywords
-
Categories
Funding
- INSERM AVENIR
- Conseil Regional d'Aquitaine
- La Fondation pour la Recherche Medicale
- ANR Projet [ANR-07-NEUR-031-01]
- FRM fellowship
- European Commission Coordination Action ENINET [LSHM-CT-200519063]
- Sequencing Facility of Bordeaux [20030304002FA, 20040305003FA]
- European Union, FEDER [2003227]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available