BARS regulates different aspect of neuronal development

MARTIN J; GASTALDI L; SOSA L; QUASSOLLO G,; RODRIGUEZ-BOULAN E; CORDA D; LUINI A; VALENTE C; CACERES A; BISBAL M

Santa Margherita di Pula

Workshop; Signalling and endomembranes; 2017

The European Molecular Biology Organization (EMBO)

Neurons are highly polarized cells typicallyextending a single long thin axon and several short, thick tapering dendrites. In neurons a preciseregulation of trafficking and targeting of membrane proteins is require to generateand maintain these different and specialized compartments. Disruptionof the endoplasmic reticulum (ER)-Golgi apparatus (GA) secretory pathway indeveloping neurons alters axon-dendritic formation. Therefore, detailedknowledge of the mechanisms underlying exiting from the GA is crucial forunderstanding neuronal polarity. In this study we have analyzed the role ofBrefeldin A-Ribosylated Substrate (BARS) in the regulation of neuronal morphologicalpolarization, the formation of dendritic Golgi outposts (GOPs) and the exit ofmembrane proteins from the TGN. The results obtained show that RNAi suppressionof BARS inhibits axonal/dendritic elongation and branching, as well as GOPs formation.In addition, using a plasma membrane (PM) proteins fused to GFP and engineeredwith reversible aggregation domains we observed that suppression or expressionof dominant negative BARS selective delay the exit of TfR and ApoEr2, twodendritic membrane proteins, from the GA without affecting trafficking of L1, atypical axonal membrane protein.  Finally,using in utero electroporation weobserved that BARS suppression results in cortical neuronal migration defects andthe generation of a bipolar polarized morphology.  Taken together, these data provide the firstset of evidence suggesting a role for BARS in neuronal polarization byregulating membrane trafficking and organelle positioning.