The planar polarity protein Scribble1 is essential for neuronal plasticity and brain function.
Journal of Neuroscience. 2010-07-21; 30(29): 9738-9752
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1. J Neurosci. 2010 Jul 21;30(29):9738-52. doi: 10.1523/JNEUROSCI.6007-09.2010.
The planar polarity protein Scribble1 is essential for neuronal plasticity and
Moreau MM(1), Piguel N, Papouin T, Koehl M, Durand CM, Rubio ME, Loll F, Richard
EM, Mazzocco C, Racca C, Oliet SH, Abrous DN, Montcouquiol M, Sans N.
(1)Molecular and Cellular Neurobiology Group, INSERM, Neurocentre Magendie,
Laboratory of Pathophysiology of Neural Plasticity, U862, 33077 Bordeaux, France,
University of Bordeaux, 33077 Bordeaux Cedex, France.
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
PMID: 20660256 [Indexed for MEDLINE]