The Core PCP Protein Prickle2 Regulates Axon Number and AIS Maturation by Binding to AnkG and Modulating Microtubule Bundling

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Sep 9

PMID 36083912

Authors

Ana Dorrego-Rivas

Jerome Ezan

Maite M Moreau

Sonia Poirault-Chassac

Nathalie Aubailly

Julie De Neve

Camille Blanchard

Francis Castets

Amelie Freal

Arne Battefeld

Nathalie Sans

Mireille Montcouquiol

Affiliations

Soon will be listed here.

Abstract

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.

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