Tetraspanins as promoters of TrkA receptor tyrosine kinase activation and biological responses of NGF

GUSTAVO PARATCHA; FACUNDO NAHUEL FERRERO RESTELLI; PAULA FONTANET; FERNANDA LEDDA

Mar del Plata, Buenos Aires

Congreso; XXXII CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS; 2017

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; and intrinsic factors, such asendogenous regulators of their receptors.Neurotrophinsare a group of secreted molecules that play a crucial role in the developmentand survival of neurons. They bind to tyrosine kinase receptors belonging tothe Trk family and promote the differentiation and survival of specificpopulations of neurons. The cooperation between Neurotrophins and other solublefactors, are mechanisms that give specificity during the development of thenervous system.Even though eachneurotrophin receptor is expressed in a different subpopulation of neurons,this alone cannot account for the specific patterns of connectivity betweenneurons and their targets. Recent studies show the importance of intrinsicfactors, which regulate the activity of these receptors and allow to broadenthe repertoire of signals induced by neurotrophins, conferring another level ofregulation and control in the establishment of neuronal connectivity.In our work,we have identified members of the Tetraspanin superfamily that regulate the NGF-mediatedTrkA signaling. We have shown by gain and loss of function assays, thatTetraspanin is a specific intrinsic regulator of TrkA activation, itsdownstream signaling and its effect on neuronal differentiation. We alsoprovide a mechanism by which Tetraspanin may be regulating the activity of TrkA