Developmental Cell
Volume 54, Issue 1, 6 July 2020, Pages 117-131.e5
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Article
Specific Isoforms of the Guanine-Nucleotide Exchange Factor dPix Couple Neuromuscular Synapse Growth to Muscle Growth

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Highlights

  • Autonomous changes in muscle growth induce scaling growth of neuromuscular synapses

  • Scaling growth is locally regulated and independent of neuronal activity

  • Insulin receptor activity promotes synapse growth through postsynaptic expansion

  • Synapse size depends on the balance between active and antagonistic dPix isoforms

Summary

Developmental growth requires coordination between the growth rates of individual tissues and organs. Here, we examine how Drosophila neuromuscular synapses grow to match the size of their target muscles. We show that changes in muscle growth driven by autonomous modulation of insulin receptor signaling produce corresponding changes in synapse size, with each muscle affecting only its presynaptic motor neuron branches. This scaling growth is mechanistically distinct from synaptic plasticity driven by neuronal activity and requires increased postsynaptic differentiation induced by insulin receptor signaling in muscle. We identify the guanine-nucleotide exchange factor dPix as an effector of insulin receptor signaling. Alternatively spliced dPix isoforms that contain a specific exon are necessary and sufficient for postsynaptic differentiation and scaling growth, and their mRNA levels are regulated by insulin receptor signaling. These findings define a mechanism by which the same signaling pathway promotes both autonomous muscle growth and non-autonomous synapse growth.

Keywords

neuromuscular junction
scaling growth
Insulin receptor
dPix
Discs-large
muscle
motor neuron
synapse

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