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BMP 依赖性突触发育需要 BMP 受体巨胞饮作用的 Abi-Abl-Rac 信号转导。

BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis.

机构信息

Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul, 08826, Korea.

Department of Neurology, Hanyang University College of Medicine, Seoul, 04763, Korea.

出版信息

Nat Commun. 2019 Feb 8;10(1):684. doi: 10.1038/s41467-019-08533-2.

DOI:10.1038/s41467-019-08533-2
PMID:30737382
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6368546/
Abstract

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.

摘要

逆行 BMP 跨突触信号对于突触发育至关重要。尽管内吞作用调节的 BMP 受体（BMPR）控制这种发育信号的重要性，但该机制仍不清楚。在这里，我们提供的证据表明，Abl 相互作用蛋白（Abi），Abl 激酶的底物和 SCAR/WAVE 复合物的组成部分，将 Abl 和 Rac1 GTPase 信号与 BMPR 巨胞饮作用联系起来，以抑制 BMP 介导的突触发育。我们发现 Abi 作用于 Abl 和 Rac1 的下游，并且 BMP 配体 Glass bottom boat（Gbb）诱导依赖 Rac1/SCAR 信号、Abl 介导的 Abi 磷酸化和 BMPR 激活的巨胞饮作用。巨胞饮作用作为突触中 BMPR 的主要内化途径，由 Gbb 激活驱动，并导致受体降解。巨胞饮作用的关键调节因子（Rabankyrin 和 CtBP）控制 BMPR 运输以限制 BMP 跨突触信号。我们得出结论，BMP 诱导的巨胞饮作用作为 BMPR 的一种稳态机制，调节 BMP 介导的突触发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/223d6691f8f7/41467_2019_8533_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/47644d4a7566/41467_2019_8533_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/5b0ddbe7c50b/41467_2019_8533_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/dd1c163f52bc/41467_2019_8533_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/0511554f833c/41467_2019_8533_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/4e465886aea3/41467_2019_8533_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/2fa4da850e24/41467_2019_8533_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/0f3a6bc5e1be/41467_2019_8533_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/223d6691f8f7/41467_2019_8533_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/47644d4a7566/41467_2019_8533_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/5b0ddbe7c50b/41467_2019_8533_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/dd1c163f52bc/41467_2019_8533_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/0511554f833c/41467_2019_8533_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/4e465886aea3/41467_2019_8533_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/2fa4da850e24/41467_2019_8533_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/0f3a6bc5e1be/41467_2019_8533_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b1/6368546/223d6691f8f7/41467_2019_8533_Fig8_HTML.jpg

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