TY - JOUR
T1 - The planar polarity protein scribble1 is essential for neuronal plasticity and brain function
AU - Moreau, Maïté M.
AU - Piguel, Nicolas
AU - Papouin, Thomas
AU - Koehl, Muriel
AU - Durand, Christelle M.
AU - Rubio, Maria E.
AU - Loll, François
AU - Richard, Elodie M.
AU - Mazzocco, Claire
AU - Racca, Claudia
AU - Oliet, Stéphane H.R.
AU - Abrous, D. Nora
AU - Montcouquiol, Mireille
AU - Sans, Nathalie
PY - 2010/7/21
Y1 - 2010/7/21
N2 - 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 Scrib1crc/+ mice might be a model for studying synaptic dysfunction and human psychiatric disorders. Copyright
AB - 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 Scrib1crc/+ mice might be a model for studying synaptic dysfunction and human psychiatric disorders. Copyright
UR - http://www.scopus.com/inward/record.url?scp=77954835232&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.6007-09.2010
DO - 10.1523/JNEUROSCI.6007-09.2010
M3 - Article
C2 - 20660256
AN - SCOPUS:77954835232
SN - 0270-6474
VL - 30
SP - 9738
EP - 9752
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 29
ER -