Novel modulators of the neurotrophic actions of NGF and its receptor TrkA

FERRERO F; FONTANET P; ALSINA FC; LEDDA F; PARATCHA G

Huerta Grande cordoba

Congreso; san 2014; 2014

SAN

Novel modulators of the neurotrophic actions of NGF and its receptor TrkA Ferrero F, Fontanet P, Alsina F, Ledda F and Paratcha G. Division of Molecular and Cellular Neuroscience-IBCN-CONICET NGF is a member of the neurotrophins, a family of growth factors critically involved in the development and function of the nervous system. It was originally described as a survival and differentiation factor of sensory and sympathetic neurons. The physiological relevance of the in vitro effects of NGF on the survival of peripheral neurons has been substantiated by the reduction in the number of sensory and sympathethic neurons observed in NGF-mutant mice. Two receptors have been identified for NGF: TrkA, high affinity receptor, and p75, low affinity receptor. Different signaling pathways are activated upon NGF binding to TrkA receptor, including those mediated by Ras/Mitogen activated kinase (MAPK), PI3-kinase (PI3K)/Akt and PLC γ. Using a cDNA microarray screening for new signaling modulators of NGF, we identified tetraspan membrane glycoproteins whose multimolecular complexes have four transmembrane domains. The aim of our study was to explore, by real-time RT-PCR and gain of function assays, the role of tetraspan glycoproteins in NGF-mediated TrkA signaling and biology. The data presented in this study suggest that tetraspans constitute a class of proteins with capacity to regulate NGF-induced neuronal differentiation.