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BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis
Retrograde BMP trans-synaptic signaling is essential for synaptic development. Despite the importance of endocytosis-regulated BMP receptor (BMPR) control of this developmental signaling, the mechanism remains unknown. Here, we provide evidence that Abelson interactor (Abi), a substrate for Abl kina...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368546/ https://www.ncbi.nlm.nih.gov/pubmed/30737382 http://dx.doi.org/10.1038/s41467-019-08533-2 |
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author | Kim, Najin Kim, Sungdae Nahm, Minyeop Kopke, Danielle Kim, Joohyung Cho, Eunsang Lee, Min-Jung Lee, Mihye Kim, Seung Hyun Broadie, Kendal Lee, Seungbok |
author_facet | Kim, Najin Kim, Sungdae Nahm, Minyeop Kopke, Danielle Kim, Joohyung Cho, Eunsang Lee, Min-Jung Lee, Mihye Kim, Seung Hyun Broadie, Kendal Lee, Seungbok |
author_sort | Kim, Najin |
collection | PubMed |
description | Retrograde BMP trans-synaptic signaling is essential for synaptic development. Despite the importance of endocytosis-regulated BMP receptor (BMPR) control of this developmental signaling, the mechanism remains unknown. Here, we provide evidence that Abelson interactor (Abi), a substrate for Abl kinase and component of the SCAR/WAVE complex, links Abl and Rac1 GTPase signaling to BMPR macropinocytosis to restrain BMP-mediated synaptic development. We find that Abi acts downstream of Abl and Rac1, and that BMP ligand Glass bottom boat (Gbb) induces macropinocytosis dependent on Rac1/SCAR signaling, Abl-mediated Abi phosphorylation, and BMPR activation. Macropinocytosis acts as the major internalization route for BMPRs at the synapse in a process driven by Gbb activation and resulting in receptor degradation. Key regulators of macropinocytosis (Rabankyrin and CtBP) control BMPR trafficking to limit BMP trans-synaptic signaling. We conclude that BMP-induced macropinocytosis acts as a BMPR homeostatic mechanism to regulate BMP-mediated synaptic development. |
format | Online Article Text |
id | pubmed-6368546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63685462019-02-11 BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis Kim, Najin Kim, Sungdae Nahm, Minyeop Kopke, Danielle Kim, Joohyung Cho, Eunsang Lee, Min-Jung Lee, Mihye Kim, Seung Hyun Broadie, Kendal Lee, Seungbok Nat Commun Article Retrograde BMP trans-synaptic signaling is essential for synaptic development. Despite the importance of endocytosis-regulated BMP receptor (BMPR) control of this developmental signaling, the mechanism remains unknown. Here, we provide evidence that Abelson interactor (Abi), a substrate for Abl kinase and component of the SCAR/WAVE complex, links Abl and Rac1 GTPase signaling to BMPR macropinocytosis to restrain BMP-mediated synaptic development. We find that Abi acts downstream of Abl and Rac1, and that BMP ligand Glass bottom boat (Gbb) induces macropinocytosis dependent on Rac1/SCAR signaling, Abl-mediated Abi phosphorylation, and BMPR activation. Macropinocytosis acts as the major internalization route for BMPRs at the synapse in a process driven by Gbb activation and resulting in receptor degradation. Key regulators of macropinocytosis (Rabankyrin and CtBP) control BMPR trafficking to limit BMP trans-synaptic signaling. We conclude that BMP-induced macropinocytosis acts as a BMPR homeostatic mechanism to regulate BMP-mediated synaptic development. Nature Publishing Group UK 2019-02-08 /pmc/articles/PMC6368546/ /pubmed/30737382 http://dx.doi.org/10.1038/s41467-019-08533-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kim, Najin Kim, Sungdae Nahm, Minyeop Kopke, Danielle Kim, Joohyung Cho, Eunsang Lee, Min-Jung Lee, Mihye Kim, Seung Hyun Broadie, Kendal Lee, Seungbok BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis |
title | BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis |
title_full | BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis |
title_fullStr | BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis |
title_full_unstemmed | BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis |
title_short | BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis |
title_sort | bmp-dependent synaptic development requires abi-abl-rac signaling of bmp receptor macropinocytosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368546/ https://www.ncbi.nlm.nih.gov/pubmed/30737382 http://dx.doi.org/10.1038/s41467-019-08533-2 |
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