EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons

Abstract The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs...

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Autores principales:	Katja Burk, John D. Murdoch, Siona Freytag, Melanie Koenig, Vinita Bharat, Ronja Markworth, Susanne Burkhardt, Andre Fischer, Camin Dean
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5db9c009a4ee437b86f567fcdc973904
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spelling	oai:doaj.org-article:5db9c009a4ee437b86f567fcdc9739042021-12-02T11:52:56ZEndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons10.1038/s41598-017-02202-42045-2322https://doaj.org/article/5db9c009a4ee437b86f567fcdc9739042017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02202-4https://doaj.org/toc/2045-2322Abstract The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes. The absence of all three EndophilinAs caused TrkB to accumulate in EEA1 and Rab7-positive endosomes, and impaired BDNF-TrkB-dependent survival signaling cascades. In addition, EndophilinA triple knockout neurons exhibited increased cell death which could not be rescued by exogenous BDNF, in a neurotrophin-dependent survival assay. Thus, EndophilinAs differentially regulate activated receptor sorting via distinct endosomal compartments to promote BDNF-dependent cell survival.Katja BurkJohn D. MurdochSiona FreytagMelanie KoenigVinita BharatRonja MarkworthSusanne BurkhardtAndre FischerCamin DeanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-19 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katja Burk John D. Murdoch Siona Freytag Melanie Koenig Vinita Bharat Ronja Markworth Susanne Burkhardt Andre Fischer Camin Dean EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons
description	Abstract The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes. The absence of all three EndophilinAs caused TrkB to accumulate in EEA1 and Rab7-positive endosomes, and impaired BDNF-TrkB-dependent survival signaling cascades. In addition, EndophilinA triple knockout neurons exhibited increased cell death which could not be rescued by exogenous BDNF, in a neurotrophin-dependent survival assay. Thus, EndophilinAs differentially regulate activated receptor sorting via distinct endosomal compartments to promote BDNF-dependent cell survival.
format	article
author	Katja Burk John D. Murdoch Siona Freytag Melanie Koenig Vinita Bharat Ronja Markworth Susanne Burkhardt Andre Fischer Camin Dean
author_facet	Katja Burk John D. Murdoch Siona Freytag Melanie Koenig Vinita Bharat Ronja Markworth Susanne Burkhardt Andre Fischer Camin Dean
author_sort	Katja Burk
title	EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons
title_short	EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons
title_full	EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons
title_fullStr	EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons
title_full_unstemmed	EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons
title_sort	endophilinas regulate endosomal sorting of bdnf-trkb to mediate survival signaling in hippocampal neurons
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5db9c009a4ee437b86f567fcdc973904
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EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons

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