A hominoid-specific signaling axis regulating the tempo of synaptic maturation.
Cell Rep
; 43(8): 114548, 2024 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-39052482
ABSTRACT
Human cortical neurons (hCNs) exhibit high dendritic complexity and synaptic density, and the maturation process is greatly protracted. However, the molecular mechanism governing these specific features remains unclear. Here, we report that the hominoid-specific gene TBC1D3 promotes dendritic arborization and protracts the pace of synaptogenesis. Ablation of TBC1D3 in induced hCNs causes reduction of dendritic growth and precocious synaptic maturation. Forced expression of TBC1D3 in the mouse cortex protracts synaptic maturation while increasing dendritic growth. Mechanistically, TBC1D3 functions via interaction with MICAL1, a monooxygenase that mediates oxidation of actin filament. At the early stage of differentiation, the TBC1D3/MICAL1 interaction in the cytosol promotes dendritic growth via F-actin oxidation and enhanced actin dynamics. At late stages, TBC1D3 escorts MICAL1 into the nucleus and downregulates the expression of genes related with synaptic maturation through interaction with the chromatin remodeling factor ATRX. Thus, this study delineates the molecular mechanisms underlying human neuron development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Transdução de Sinais
/
Proteínas dos Microfilamentos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
/
Cell reports
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos