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Kim, N., Kim, S., Nahm, M., Kopke, D., Kim, J., Cho, E., Lee, M.J., Lee, M., Kim, S.H., Broadie, K., Lee, S. (2019). BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis.  Nat. Commun. 10(1): 684.
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Research paper

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.

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PMC6368546 (PMC) (EuropePMC)
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    Nat. Commun.
    Nature communications
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