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

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

Author information

1
Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul, 08826, Korea.
2
Department of Neurology, Hanyang University College of Medicine, Seoul, 04763, Korea.
3
Departments of Biological Sciences, Cell and Developmental Biology, and Pharmacology, Vanderbilt Brain Institute, Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, 37232, USA.
4
Department of Brain and Cognitive Sciences, Seoul National University, Seoul, 08826, Korea.
5
Department of Cell and Developmental Biology and Dental Research Institute, Seoul National University, Seoul, 08826, Korea.
6
Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul, 08826, Korea. seunglee@snu.ac.kr.
7
Department of Brain and Cognitive Sciences, Seoul National University, Seoul, 08826, Korea. seunglee@snu.ac.kr.
8
Department of Cell and Developmental Biology and Dental Research Institute, Seoul National University, Seoul, 08826, Korea. seunglee@snu.ac.kr.

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.

PMID:
30737382
PMCID:
PMC6368546
DOI:
10.1038/s41467-019-08533-2
[Indexed for MEDLINE]
Free PMC Article

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