ADP ribosylation factor 6 regulates neuronal migration in the developing cerebral cortex through FIP3/arfophilin-1-dependent endosomal trafficking of N-cadherin

Yoshinobu Hara, Masahiro Fukaya, Kanehiro Hayashi, Takeshi Kawauchi, Kazunori Nakajima, Hiroyuki Sakagami

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

During neural development, endosomal trafficking controls cell shape and motility through the polarized transport of membrane proteins related to cellcell and cellextracellular matrix interactions. ADP ribosylation factor 6 (Arf6) is a critical small GTPase that regulates membrane trafficking between the plasma membrane and endosomes. We herein demonstrated that the knockdown of endogenous Arf6 in mouse cerebral cortices led to impaired neuronal migration in the intermediate zone and cytoplasmic retention of N-cadherin and syntaxin12 in migrating neurons. Rescue experiments with separation-of-function Arf6 mutants identified Rab11 familyinteracting protein 3 (FIP3)/Arfophilin-1, a dual effector for Arf6 and Rab11, as a downstream effector of Arf6 in migrating neurons. The knockdown of FIP3 led to impaired neuronal migration in the intermediate zone and cytoplasmic retention of N-cadherin in migrating neurons, similar to that of Arf6, which could be rescued by the coexpression of wild-type FIP3 but not FIP3 mutants lacking the binding site for Arf6 or Rab11. These results suggest that Arf6 regulates cortical neuronal migration in the intermediate zone through the FIP3-dependent endosomal trafficking.

Original languageEnglish
Article numbere0148-16.2016
JournaleNeuro
Volume3
Issue number4
DOIs
Publication statusPublished - 2016

Keywords

  • Arf6
  • Layer formation
  • Membrane trafficking
  • Migration
  • N-cadherin
  • Receptor recycling

ASJC Scopus subject areas

  • Neuroscience(all)

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