Tetraspanin promotes NGF signaling by controlling TrkA receptor proteostasis

FERRERO RESTELLI, FACUNDO; PARATCHA, GUSTAVO; LEDDA, FERNANDA; FONTANET, PAULA ALDANA

Córdoba

Congreso; XXXIII CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS; 2019

Sociedad Argentina de Investigación en Neurociencias (SAN)

A keyquestion in developmental neurobiology is understanding how axons and dendritesfrom different neuronal populations develop to generate specific patterns ofneuronal connectivity. This process is regulated by the interaction ofextrinsic signals, such as neurotrophins (NTs); and intrinsic factors, such asendogenous regulators of their receptors.NTs are agroup of secreted molecules that play a crucial role in the development andsurvival of neurons. They bind to tyrosine kinase receptors belonging to theTrk family and promote the differentiation and survival of specific populationsof neurons. The cooperation between NTs and other soluble factors, aremechanisms that give specificity during the development of the nervous system.Recentstudies also show the importance of intrinsic factors, which regulate theactivity of these receptors and allow to broaden the repertoire of signalsinduced by NTs, conferring another level of regulation and control in theestablishment of neuronal connectivity.In our work,we have identified members of the Tetraspanin superfamily that regulate the NGF-mediatedTrkA signaling. We have shown that Tetraspanin is a specific intrinsicregulator of TrkA activation, its downstream signaling and its effect on neuronaldifferentiation. We also provide a novel homeostatic mechanism to controlbiosynthetic trafficking and degradation of TrkA.