The planar polarity protein Scribble1 is essential for neuronal plasticity and brain function.
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.
Moreau
Maïté M
MM
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.
Piguel
Nicolas
N
Papouin
Thomas
T
Koehl
Muriel
M
Durand
Christelle M
CM
Rubio
Maria E
ME
Loll
François
F
Richard
Elodie M
EM
Mazzocco
Claire
C
Racca
Claudia
C
Oliet
Stéphane H R
SH
Abrous
D Nora
DN
Montcouquiol
Mireille
M
Sans
Nathalie
N
D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D023421:Models, Animal; D009043:Motor Activity / Q000502:physiology; D009154:Mutation; D009473:Neuronal Plasticity / Q000235:genetics*; D018408:Patch-Clamp Techniques; D012919:Social Behavior; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; C508433:scrib protein, mouse