SARA participation as a negative regulator of the TGF β si gnaling pathway in neuronal development

ROZÉS-SALVADOR, VICTORIA; SEBASTIÁN OMAR SIRI; CONDE, CECILIA

Cordoba

Congreso; SAN; 2018

Sociedad Argentina de Neurociencia

Severalevents are necessary for proper neuronal development, such as cytoskeletaldynamics and endosomal trafficking. Smad Anchor for Receptor Activ ation (SARA)is a protein that binds to early endosomes; carrying out specific functionsrelated to traffic but also participating in signaling such as TGF βpathway. It has been described that SARA recruits Smad2/3 and, therefore,favors the activation of the pathway in epithelial cells. Moreover, it has beenshown that TGF β signaling specifies axon during neuronaldevelopment; however, SARA participation in this signaling pathway during thedevelopmental process remains unknown. For this reason we proposed to analyzethe role of SARA in the TGF β signaling during neuronal development.Preliminary results in hippocampal neurons, through FRET AcceptorPhotobleaching showed interaction between SARA and the TGF βreceptor. Also, performing loss and gain of functi on experiments, SARAsupression (through shRNA expression) generates both greater axonal growth andloss of axonal specification since neurons have more than one axon comparedwith the control. Interestingly, this same phenotype is obtained when we use am utant form of SARA that prevents its binding to PP1c protein and therefore,the T β RIremains hyperphosphorylated, keeping the pathway activated.These resultssuggest that SARA participates in TGF β pathway in neurons through the negativeregulation, which seems to be a requirement for the correct neuronaldevelopment