Tspan1 como un regulador clave de la actividad neurotrófica del receptor TrkA
In this thesis we identify and characterize a novel modulatory mechanism to control neurotrophin receptor activation in developing neurons, as a way to understand the mechanism that underlie neuronal homeostasis and physiology.\nWe demonstrate that the protein Tetraspanin 1 (Tspan1) is a critical re...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2019
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_5907 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_5907.dir/5907.PDF |
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| Sumario: | In this thesis we identify and characterize a novel modulatory mechanism to control neurotrophin receptor activation in developing neurons, as a way to understand the mechanism that underlie neuronal homeostasis and physiology.\nWe demonstrate that the protein Tetraspanin 1 (Tspan1) is a critical regulator of TrkA signaling and neuronal differentiation induced by NGF. Tspan1 is expressed by developing TrkA-positive dorsal root ganglion (DRG) neurons and its downregulation leads to a diminished axonal growth in response to NGF. Additionally, our results demonstrate that Tspan1 interacts specifically in vivo and in vitro with the immature form of TrkA localized in the endoplasmic reticulum (ER). Finally, knockdown of Tspan1 reduces TrkA surface levels and promotes its sorting to the lysosomal/autophagic degradation pathway.\nAltogether, our data establish a novel homeostatic role of Tspan1 as a key regulator of TrkA proteostasis, coordinating its maturation, biosynthetic trafficking and degradation, thereby promoting NGF signaling. |
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