BARS Influences Neuronal Development by Regulation of Post-Golgi Trafficking

LAURA GASTALDI; JOSEFINA INÉS MARTÍN; LUCAS J. SOSA; GONZALO QUASSOLLO; YAEL MACARENA PERALTA CUASOLO; CARMEN VALENTE; ALBERTO LUINI; DANIELA CORDA; ALFREDO CÁCERES; MARIANO BISBAL

Cells

MARY ANN LIEBERT INC

Lugar: New York; Año: 2022

2073-4409

Neurons are highly polarized cells requiring precise regulation of trafficking and targetingof membrane proteins to generate and maintain different and specialized compartments, such as axonsand dendrites. Disruption of the Golgi apparatus (GA) secretory pathway in developing neuronsalters axon/dendritic formation. Therefore, detailed knowledge of the mechanisms underlyingvesicles exiting from the GA is crucial for understanding neuronal polarity. In this study, we analyzedthe role of Brefeldin A-Ribosylated Substrate (CtBP1-S/BARS), a member of the C-terminal-bindingprotein family, in the regulation of neuronal morphological polarization and the exit of membraneproteins from the Trans Golgi Network. Here, we show that BARS is expressed during neuronaldevelopment in vitro and that RNAi suppression of BARS inhibits axonal and dendritic elongationin hippocampal neuronal cultures as well as largely perturbed neuronal migration and multipolarto-bipolar transition during cortical development in situ. In addition, using plasma membrane(PM) proteins fused to GFP and engineered with reversible aggregation domains, we observed thatexpression of fission dominant-negative BARS delays the exit of dendritic and axonal membraneprotein-containing carriers from the GA. Taken together, these data provide the first set of evidencesuggesting a role for BARS in neuronal development by regulating post-Golgi membrane trafficking.