Regulation of TRKA expression by BEX3

Abstract

Resumen del póster presentado a l 15º Congreso Nacional de la Sociedad Española de Neurociencia (SENC) celebrado en Oviedo del 25 al 27 de septiembre de 2013.TrkA protein levels are tightly regulated during development to ensure the survival of NGF-dependent neurons. Using a yeast two-hybrid screening, we have found an interaction of TrkA with Bex3 (Brain Expressed X-linked gene), a protein that has been previously described to interact with p75NTR. Bex3 protein contains a leucine-rich nuclear export sequence, two boxes for ubiquitination and a CaaX box. The association between TrkA and Bex3 occurs through the juxtamembrane region of TrkA and the C-terminus of Bex3. Bex3 is expressed in the same DRG neurons that express TrkA but prior to it. Interestingly, Bex3 depletion led to a decrease of protein and mRNA TrkA levels in sensory neurons but not of TrkB levels in hippocampal neurons. Using reporter and ChIP assays we have observed that Bex3 modulates and binds to trkA gene promoter. In addition, Bex3 translocates from cytoplasm to nucleus and we noticed that in response to NGF, Bex3 dimerizes and accumulates in nucleus. Finally, we have observed that Bex3 levels regulate the survival of NGF-dependent sensory neurons. These findings indicate that Bex3 protein modulates TrkA levels through the regulation of the gene´s promoter.Peer reviewe