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Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth

Neurotrophins, such as NGF and BDNF, induce sustained activation of Rap1 small G protein and ERK, which are essential for neurite outgrowth. We show involvement of a GDP/GTP exchange factor (GEF) for Rap1, PDZ-GEF1, in these processes. PDZ-GEF1 is activated by GTP-Rap1 via a positive feedback mechan...

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Autores principales: Hisata, Shu, Sakisaka, Toshiaki, Baba, Takeshi, Yamada, Tomohiro, Aoki, Kazuhiro, Matsuda, Michiyuki, Takai, Yoshimi
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064548/
https://www.ncbi.nlm.nih.gov/pubmed/17724123
http://dx.doi.org/10.1083/jcb.200610073
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author Hisata, Shu
Sakisaka, Toshiaki
Baba, Takeshi
Yamada, Tomohiro
Aoki, Kazuhiro
Matsuda, Michiyuki
Takai, Yoshimi
author_facet Hisata, Shu
Sakisaka, Toshiaki
Baba, Takeshi
Yamada, Tomohiro
Aoki, Kazuhiro
Matsuda, Michiyuki
Takai, Yoshimi
author_sort Hisata, Shu
collection PubMed
description Neurotrophins, such as NGF and BDNF, induce sustained activation of Rap1 small G protein and ERK, which are essential for neurite outgrowth. We show involvement of a GDP/GTP exchange factor (GEF) for Rap1, PDZ-GEF1, in these processes. PDZ-GEF1 is activated by GTP-Rap1 via a positive feedback mechanism. Upon NGF binding, the TrkA neurotrophin receptor is internalized from the cell surface, passes through early endosomes, and arrives in late endosomes. A tetrameric complex forms between PDZ-GEF1, synaptic scaffolding molecule and ankyrin repeat-rich membrane spanning protein which interacts directly with the TrkA receptor. At late endosomes, the complex induces sustained activation of Rap1 and ERK, resulting in neurite outgrowth. In cultured rat hippocampal neurons, PDZ-GEF1 is recruited to late endosomes in a BDNF-dependent manner involved in BDNF-induced neurite outgrowth. Thus, the interaction of PDZ-GEF1 with an internalized neurotrophin receptor transported to late endosomes induces sustained activation of both Rap1 and ERK and neurite outgrowth.
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spelling pubmed-20645482008-02-27 Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth Hisata, Shu Sakisaka, Toshiaki Baba, Takeshi Yamada, Tomohiro Aoki, Kazuhiro Matsuda, Michiyuki Takai, Yoshimi J Cell Biol Research Articles Neurotrophins, such as NGF and BDNF, induce sustained activation of Rap1 small G protein and ERK, which are essential for neurite outgrowth. We show involvement of a GDP/GTP exchange factor (GEF) for Rap1, PDZ-GEF1, in these processes. PDZ-GEF1 is activated by GTP-Rap1 via a positive feedback mechanism. Upon NGF binding, the TrkA neurotrophin receptor is internalized from the cell surface, passes through early endosomes, and arrives in late endosomes. A tetrameric complex forms between PDZ-GEF1, synaptic scaffolding molecule and ankyrin repeat-rich membrane spanning protein which interacts directly with the TrkA receptor. At late endosomes, the complex induces sustained activation of Rap1 and ERK, resulting in neurite outgrowth. In cultured rat hippocampal neurons, PDZ-GEF1 is recruited to late endosomes in a BDNF-dependent manner involved in BDNF-induced neurite outgrowth. Thus, the interaction of PDZ-GEF1 with an internalized neurotrophin receptor transported to late endosomes induces sustained activation of both Rap1 and ERK and neurite outgrowth. The Rockefeller University Press 2007-08-27 /pmc/articles/PMC2064548/ /pubmed/17724123 http://dx.doi.org/10.1083/jcb.200610073 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Hisata, Shu
Sakisaka, Toshiaki
Baba, Takeshi
Yamada, Tomohiro
Aoki, Kazuhiro
Matsuda, Michiyuki
Takai, Yoshimi
Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth
title Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth
title_full Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth
title_fullStr Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth
title_full_unstemmed Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth
title_short Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth
title_sort rap1-pdz-gef1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of rap1 and erk and neurite outgrowth
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064548/
https://www.ncbi.nlm.nih.gov/pubmed/17724123
http://dx.doi.org/10.1083/jcb.200610073
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