The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Science Advances Année : 2022

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

Ana Dorrego-Rivas
Jerome Ezan
Maïté Moreau
  • Fonction : Auteur
Sonia Poirault-Chassac
  • Fonction : Auteur
Nathalie Aubailly
  • Fonction : Auteur
Julie de Neve
Camille Blanchard
  • Fonction : Auteur
Amélie Fréal
  • Fonction : Auteur
Arne Battefeld
Nathalie Sans
Mireille Montcouquiol

Résumé

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.

Dates et versions

hal-03856056 , version 1 (16-11-2022)

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Citer

Ana Dorrego-Rivas, Jerome Ezan, Maïté Moreau, Sonia Poirault-Chassac, Nathalie Aubailly, et al.. The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling. Science Advances , 2022, 8 (36), ⟨10.1126/sciadv.abo6333⟩. ⟨hal-03856056⟩
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