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Nat. Commun., Published 08 February 2019, 10, Article number: 684 | https://doi.org/10.1038/s41467-019-08533-2 BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis

Najin Kim¹, Sungdae Kim¹, Minyeop Nahm², Danielle Kopke³, Joohyung Kim⁴, Eunsang Cho⁴, Min-Jung Lee⁵, Mihye Lee⁵, Seung Hyun Kim², Kendal Broadie³ & Seungbok Lee^1,4,5,*

¹Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul 08826, Korea. ²Department of Neurology, Hanyang University College of Medicine, Seoul 04763, Korea. ³Departments 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. ⁴Department of Brain and Cognitive Sciences, Seoul National University, Seoul 08826, Korea. ⁵Department of Cell and Developmental Biology and Dental Research Institute, Seoul National University, Seoul 08826, Korea. These authors contributed equally: Najin Kim, Sungdae Kim, Minyeop Nahm.

^*Correspondence and requests for materials should be addressed to S.L.

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.

논문정보

형식Research article
게재일2019년 02월 (BRIC 등록일 2019-02-19)
연구진국내(교신)+국외 연구진
분야 의약학 > 분자세포의학

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