Tuba activates cdc42 during neuronal polarization downstream of the small gtpase rab8a

Pamela J. Urrutia, Felipe Bodaleo, Daniel A. Bórquez, Yuta Homma, Victoria Rozes-Salvador, Cristopher Villablanca, Cecilia Conde, Mitsunori Fukuda, Christian González-Billault

Research output: Contribution to journalArticlepeer-review

Abstract

The acquisition of neuronal polarity is a complex molecular process that depends on changes in cytoskeletal dynamics and directed membrane traffic, regulated by the Rho and Rab families of small GTPases, respectively. However, during axon specification, a molecular link that couples these protein families has yet to be identified. In this paper, we describe a new positive feedback loop between Rab8a and Cdc42, coupled by Tuba, a Cdc42-specific guanine nucleotide-exchange factor (GEF), that ensures a single axon generation in rodent hippocampal neurons from embryos of either sex. Accordingly, Rab8a or Tuba gain-of-function generates neurons with supernumerary axons whereas Rab8a or Tuba loss-of-function abrogated axon specification, phenocopying the well-established effect of Cdc42 on neuronal polarity. Although Rab8 and Tuba do not interact physically, the activity of Rab8 is essential to generate a proximal to distal axonal gradient of Tuba in cultured neurons. Tuba-associated and Rab8a-associated polarity defects are also evidenced in vivo, since dominant negative (DN) Rab8a or Tuba knock-down impairs cortical neuronal migration in mice. Our results suggest that Tuba coordinates directed vesicular traffic and cytoskeleton dynamics during neuronal polarization.

Original languageEnglish
Pages (from-to)1636-1649
Number of pages14
JournalJournal of Neuroscience
Volume41
Issue number8
DOIs
Publication statusPublished - 2021 Feb 24

Keywords

  • Axon specification
  • Cytoskeleton
  • Neuronal differentiation
  • Neuronal polarity
  • Rab gtpases
  • Rho gtpases

ASJC Scopus subject areas

  • Neuroscience(all)

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