Development
Author: Juan Manuel Bourbotte Asensio | email: jbourbotte@immf.uncor.edu
Juan Manuel Bourbotte Asensio 1°, Victoria Rozés-Salvador 2°, Cecilia Conde 1°
1° INIMEC-UNC-CONICET
2° CIBICI-CONICET
SSARA (Smad Anchor for Receptor Activation) is a scaffold protein that recruits Smads 2/3 to the TGFβ-activated receptor I (Transforming Growth Factor Beta-TβRI). Previously, we have demonstrated that SARA localizes at early endosomes (EEs), modulates the proper delivery to somatodendritic and axonal proteins, and participates in neuronal migration during neocortical development. Recently, we have identified to SARA as a negative regulator of the TGFβ pathway. In this work, we focus on the biological role of SARA and its potential association with the TGFβ pathway, during the development of sensory neurons (peripheral nervous system). In embryonic dorsal root ganglion (DRG) neurons, TβRI and SARA are endogenously expressed at the early stages of development and interact in the EEs. The addition of TGFβ enhances this interaction. SARA suppression or exogenous stimulation of the TGFβ pathway promotes axonal growth in embryonic DRGs. Moreover, in postnatal DRGs, TGFβ treatment induces both neuritic elongation and branching and a reduction in the size of growth cones, during axonal regrowth. In addition, TGFβ treatment increases SARA expression together with the number and distribution of SARA endosomes both at the soma and axon level. In summary, our results provide evidence on the involvement of SARA in the TGFβ signalling in axonal growth and regrowth of sensory neurons, highlighting mechanisms and molecules that regulate key physiological processes of neurodevelopment.