Involvement of SARA in axon/dendrite formation and cortical layer lamination

MESTRES LASCANO I; ARIAS C; SUNG CH; CÁCERES A; CONDE C

Workshop; Emerging Concepts on Neuronal Cytoskeleton; 2013

It has been reported that in cell lines SARA (Smad Anchor for Receptor Activation) plays a crucial role in Rab5-mediated endocytosis. SARA localizes to early endosomes (EE) where it regulates their morphology and function. We analyzed the role of SARA during neuronal development. In primary cultured neurons SARA over-expression generates unusual large EE and reduces neurite outgrowth, whereas SARA suppression with short hairpin RNAi results in the appearance of a large Rab11 positive recycling compartment and long axons with large growth cones. In situ electroporation (IUE) of mouse embryonic brain also suggests a pivotal role for SARA in nerve cell development. After IUE control Hc-Red transfected neurons migrate through the cortical plate showing proper pia-directed orientation. By contrast, neurons expressing Hc-Red-sh-SARA fail to migrate properly, acquiring a horizontal orientation. Quantitative analysis reveals that 90% of these neurons lack vertical orientation, being tilted with angles ranging from 0 to 45 degrees. Together, our results suggest a major contribution of SARA to key aspects of neuronal development including migration, neurite formation and polarized growth. It is likely that some of these functions are related with the role of SARA as a regulator of endosomal trafficking.