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

Author

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  • Najin Kim

    (Seoul National University)

  • Sungdae Kim

    (Seoul National University)

  • Minyeop Nahm

    (Hanyang University College of Medicine)

  • Danielle Kopke

    (Vanderbilt Brain Institute, Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University)

  • Joohyung Kim

    (Seoul National University)

  • Eunsang Cho

    (Seoul National University)

  • Min-Jung Lee

    (Seoul National University)

  • Mihye Lee

    (Seoul National University)

  • Seung Hyun Kim

    (Hanyang University College of Medicine)

  • Kendal Broadie

    (Vanderbilt Brain Institute, Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University)

  • Seungbok Lee

    (Seoul National University
    Seoul National University
    Seoul National University)

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.

Suggested Citation

  • Najin Kim & Sungdae Kim & Minyeop Nahm & Danielle Kopke & Joohyung Kim & Eunsang Cho & Min-Jung Lee & Mihye Lee & Seung Hyun Kim & Kendal Broadie & Seungbok Lee, 2019. "BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08533-2
    DOI: 10.1038/s41467-019-08533-2
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