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The HSPG Glypican Regulates Experience-Dependent Synaptic and Behavioral Plasticity by Modulating the Non-Canonical BMP Pathway.

Cell Rep. 2019 Sep 17;28(12):3144-3156.e4
Keisuke Kamimura 1 , Aiko Odajima 2 , Yuko Ikegawa 2 , Chikako Maru 2 , Nobuaki Maeda 3
Keisuke Kamimura 1 , Aiko Odajima 2 , Yuko Ikegawa 2 , Chikako Maru 2 , Nobuaki Maeda 3

[No authors listed]

Author information
  • 1 Neural Network Project, Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan. Electronic address: kamimura-ks@igakuken.or.jp.
  • 2 Neural Network Project, Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
  • 3 Neural Network Project, Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan. Electronic address: maeda-nb@igakuken.or.jp.

摘要


Under food deprivation conditions, Drosophila larvae exhibit increases in locomotor speed and synaptic bouton numbers at neuromuscular junctions (NMJs). Octopamine, the invertebrate counterpart of noradrenaline, plays critical roles in this process; however, the underlying mechanisms remain unclear. We show here that a glypican (Dlp) negatively regulates type I synaptic bouton formation, postsynaptic expression of GluRIIA, and larval locomotor speed. Starvation-induced octopaminergic signaling decreases Dlp expression, leading to increases in synapse formation and locomotion. Dlp is expressed by postsynaptic muscle cells and suppresses the non-canonical BMP pathway, which is composed of the presynaptic BMP receptor Wit and postsynaptic GluRIIA-containing ionotropic glutamate receptor. We find that during starvation, decreases in Dlp increase non-canonical BMP signaling, leading to increases in GluRIIA expression, type I bouton number, and locomotor speed. Our results demonstrate that octopamine controls starvation-induced neural plasticity by regulating Dlp and provides insights into how proteoglycans can influence behavioral and synaptic plasticity.

KEYWORDS: BMP signaling, Drosophila melanogaster, glutamate receptor, glypican, heparan sulfate proteoglycan, neuromuscular junction, octopamine, synaptic plasticity