Tetraspanin promotes NGF signaling by controlling TrkA receptor proteostasis

FERRERO RESTELLI, FACUNDO; PARATCHA GUSTAVO; LEDDA, FERNANDA; DE VINCENTI ANA PAULA

Córdoba

Congreso; XXXIII CONGRESO ANUAL SAN 2018; 2018

A key question in developmental neurobiology is understanding how axons and dendrites from different neuronal populations develop to generate specific patterns of neuronal connectivity. This process is regulated by the interaction of extrinsic signals, such as neurotrophins (NTs); and intrinsic factors, such as endogenous regulators of their receptors.NTs are a group of secreted molecules that play a crucial role in the development and survival of neurons. They bind to tyrosine kinase receptors belonging to the Trk family and promote the differentiation and survival of specific populations of neurons. The cooperation between NTs and other soluble factors, are mechanisms that give specificity during the development of the nervous system.Recent studies also show the importance of intrinsic factors, which regulate the activity of these receptors and allow to broaden the repertoire of signals induced by NTs, conferring another level of regulation and control in the establishment of neuronal connectivity.In our work, we have identified members of the Tetraspanin superfamily that regulate the NGF-mediated TrkA signaling. We have shown that Tetraspanin is a specific intrinsic regulator of TrkA activation, its downstream signaling and its effect on neuronal differentiation. We also provide a novel homeostatic mechanism to control biosynthetic trafficking and degradation of TrkA.