BARS regulates different aspect of neuronal development

MARTÍN J; GASTALDI L; LUCAS J. SOSA; QUASSOLLO G; RODRIGUEZ-BOULAN E; CORDA D; LUINI A; VALENTE C; CACERES A; MARIANO BISBAL

San Feliu de Guixols

Conferencia; Cell polarity and membrane conference; 2017

EMBO

Neurons are highly polarized cells typically extending a single long thin axon and several short, thick tapering dendrites. In neurons a precise regulation of trafficking and targeting of membrane proteins is require to generate and maintain these different and specialized compartments. Disruption of the endoplasmic reticulum (ER)-Golgi apparatus (GA) secretory pathway in developing neurons alters axon-dendritic formation. Therefore, detailed knowledge of the mechanisms underlying exiting from the GA is crucial for understanding neuronal polarity. In this study we have analyzed the role of Brefeldin A-Ribosylated Substrate (BARS) in the regulation of neuronal morphological polarization, the formation of dendritic Golgi outposts (GOPs) and the exit of membrane proteins from the TGN. The results obtained show that RNAi suppression of BARS inhibits axonal/dendritic elongation and branching, as well as GOPs formation. In addition, using a plasma membrane (PM) proteins fused to GFP and engineered with reversible aggregation domains we observed that suppression or expression of dominant negative BARS selective delay the exit of TfR and ApoEr2, two dendritic membrane proteins, from the GA without affecting trafficking of L1, a typical axonal membrane protein. Finally, using in utero electroporation we observed that BARS suppression results in cortical neuronal migration defects and the generation of a bipolar polarized morphology. Taken together, these data provide the first set of evidence suggesting a role for BARS in neuronal polarization by regulating membrane trafficking and organelle positioning.