Role of SARA in the regulation of endocytic and membrane trafficking processes during neuronal development.

VICTORIA ROZÉS SALVADOR; SEBASTIAN SIRI; CECILIA CONDE

Dresden, Alemania

Otro; EMBO Practical Course on Mouse Genome Engineering; 2017

EMBO

In mammal cells, endocytic membrane traffic plays an essential role in delivering membrane components, receptor-associated ligands and solute molecules to intracellular destinations. The endosomal pathway is known to play a decisive role in many neurodevelopment processes, including migration, polarization and synaptic function. Smad Anchor for Receptor Protein (SARA) is an early endosomal (EE) protein that acts as a downstream effector of Rab5-mediated EE fusion. Previous studies of the lab show that SARA-overexpression generates enlargement of EEs and neurons with short neurites. Contrary, SARA-silenced neurons shows enlargement or aggregates of recycling endosomes (RE) Rab11+, multiple axons and an increase in the growth cones size. Also, SARA is enriched at the apical endfeet of radial glia of mouse neocortex. While silencing SARA did not lead to detectable neurogenic phenotypes, SARA-suppressed neurons exhibit impaired orientation and migration across the intermediate zone, suggesting that SARA regulates the orientation, multipolar-to-bipolar transition, and positioning of cortical neurons via modulating surface L1 expression. Preliminary results in cultures of hippocampal neurons transfected with the mutant form of SARA (SARA F728) that maintains hyperphosphorylated TGFβRI receptor, show an increase in the number of SARA + endosomes and smaller size. In addition, they show an acceleration in the transition between stage 1 and stage 2 of that neurons. We propose to analyze if SARA regulation on endosomal system is related to membrane expansion process during neuronal development through TGFβ.This will help us understand dynamics of the components of the endocytic pathway and its regulation during neuronal development.