info:eu-repo/semantics/article
Tuba activates cdc42 during neuronal polarization downstream of the small gtpase rab8a
Fecha
2021-02Registro en:
Urrutia, Pamela J; Bodaleo, Felipe; Bórquez, Daniel A.; Homma, Yuta; Rozés Salvador, María Victoria; et al.; Tuba activates cdc42 during neuronal polarization downstream of the small gtpase rab8a; Society for Neuroscience; Journal of Neuroscience; 41; 8; 2-2021; 1636-1649
0270-6474
1529-2401
CONICET Digital
CONICET
Autor
Urrutia, Pamela J
Bodaleo, Felipe
Bórquez, Daniel A.
Homma, Yuta
Rozés Salvador, María Victoria
Villablanca, Cristopher
Conde, Cecilia Beatriz
Fukuda, Mitsunori
González Billault, Christian
Resumen
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.