RGD Reference Report - TBC1D24 regulates neuronal migration and maturation through modulation of the ARF6-dependent pathway. - Rat Genome Database

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TBC1D24 regulates neuronal migration and maturation through modulation of the ARF6-dependent pathway.

Authors: Falace, A  Buhler, E  Fadda, M  Watrin, F  Lippiello, P  Pallesi-Pocachard, E  Baldelli, P  Benfenati, F  Zara, F  Represa, A  Fassio, A  Cardoso, C 
Citation: Falace A, etal., Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2337-42. doi: 10.1073/pnas.1316294111. Epub 2014 Jan 27.
RGD ID: 11537391
Pubmed: (View Article at PubMed) PMID:24469796
DOI: Full-text: DOI:10.1073/pnas.1316294111

Alterations in the formation of brain networks are associated with several neurodevelopmental disorders. Mutations in TBC1 domain family member 24 (TBC1D24) are responsible for syndromes that combine cortical malformations, intellectual disability, and epilepsy, but the function of TBC1D24 in the brain remains unknown. We report here that in utero TBC1D24 knockdown in the rat developing neocortex affects the multipolar-bipolar transition of neurons leading to delayed radial migration. Furthermore, we find that TBC1D24-knockdown neurons display an abnormal maturation and retain immature morphofunctional properties. TBC1D24 interacts with ADP ribosylation factor (ARF)6, a small GTPase crucial for membrane trafficking. We show that in vivo, overexpression of the dominant-negative form of ARF6 rescues the neuronal migration and dendritic outgrowth defects induced by TBC1D24 knockdown, suggesting that TBC1D24 prevents ARF6 activation. Overall, our findings demonstrate an essential role of TBC1D24 in neuronal migration and maturation and highlight the physiological relevance of the ARF6-dependent membrane-trafficking pathway in brain development.

Annotation

Gene Ontology Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Tbc1d24  (TBC1 domain family, member 24)


Additional Information