DORREGO RIVAS, Ana; EZAN, Jerome; MOREAU, Maite; POIRAULT-CHASSAC, Sonia; AUBAILLY, Nathalie; DE NEVE, Julie; BLANCHARD, Camille; CASTETS, Francis; FREAL, Amelie; BATTEFELD, Arne; SANS, Nathalie; MONTCOUQUIOL, Mireille

doi:10.1126/sciadv.abo6333

Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

EZAN, Jerome

Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

MOREAU, Maite

Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

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Science Advances. 2022-09-09, vol. 8, n° 36

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Core planar cell polarity (PCP) genes, which are involved in various neurodevelopmental disorders such as neural tube closure, epilepsy, and autism spectrum disorder, have poorly defined molecular signatures in neurons, mostly synapse-centric. Here, we show that the core PCP protein Prickle-like protein 2 (Prickle2) controls neuronal polarity and is a previously unidentified member of the axonal initial segment (AIS) proteome. We found that Prickle2 is present and colocalizes with AnkG480, the AIS master organizer, in the earliest stages of axonal specification and AIS formation. Furthermore, by binding to and regulating AnkG480, Prickle2 modulates its ability to bundle microtubules, a crucial mechanism for establishing neuronal polarity and AIS formation. Prickle2 depletion alters cytoskeleton organization, and Prickle2 levels determine both axon number and AIS maturation. Last, early Prickle2 depletion produces impaired action potential firing.< Leer menos

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https://oskar-bordeaux.fr/handle/20.500.12278/172309

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http://dx.doi.org/10.1126/sciadv.abo6333

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Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043

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The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling

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The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling

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URI

DOI

Proyecto ANR

Centros de investigación