Proneurotrophin-3 may induce Sortilin-dependent death in inner ear neurons

Autor:	Peder Madsen, Pernille Jansen, Jens R. Nyengaard, Erik Ilsø Christensen, Anders Nykjaer, Kenneth K. Teng, Camilla Gustafsen, Claus Munck Petersen, Therese Ovesen, Jacob Tauris, Elisabeth Schwarz
Rok vydání:	2011
Předmět:	Brain-derived neurotrophic factor biology General Neuroscience HEK 293 cells Neurotrophin-3 medicine.anatomical_structure nervous system Downregulation and upregulation biology.protein medicine Low-affinity nerve growth factor receptor Inner ear sense organs Neuroscience Spiral ganglion Neurotrophin
Zdroj:	European Journal of Neuroscience. 33:622-631
ISSN:	0953-816X
Popis:	The precursor of the neurotrophin NGF (proNGF) serves physiological functions distinct from its mature counterpart as it induces neuronal apoptosis through activation of a p75 neurotrophin receptor (p75 NTR ) and Sortilin death-signalling complex. The neurotrophins BDNF and NT3 provide essential trophic support to auditory neurons. Injury to the neurotrophin secreting cells in the inner ear is followed by irreversible degeneration of spiral ganglion neurons with consequences such as impaired hearing or deafness. Lack of mature neurotrophins may explain the degeneration of spiral ganglion neurons, but another mechanism is possible since unprocessed proNTs released from the injured cells may contribute to the degeneration by induction of apoptosis. Recent studies demonstrate that proBDNF, like proNGF, is a potent inducer of Sortilin:p75 NTR mediated apoptosis. In addition, a coincident upregulation of proBDNF and p75 NTR has been observed in degenerating spiral ganglion neurons, but the Sortilin expression in the inner ear is unresolved. Here we demonstrate that Sortilin and p75 NTR are coexpressed in neurons of the neonatal inner ear. Furthermore, we establish that proNT3 exhibits high affinity binding to Sortilin and has the capacity to enhance cell surface Sortilin:p75 NTR complex formation as well as to mediate apoptosis in neurons coexpressing p75 NTR and Sortilin. Based on examination of wt and Sortilin deficient mouse embryos, Sortilin does not significantly influence the developmental selection of spiral ganglion neurons. However, our results suggest that proNT3 and proBDNF may play important roles in the response to noise-induced injuries or ototoxic damage via the Sortilin:p75 NTR death-signalling complex.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::614f2c22e6bb0bbfc1fdc87822334c91 https://doi.org/10.1111/j.1460-9568.2010.07556.x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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