Mayday sustains trans-synaptic BMP signaling required for synaptic maintenance with age.

Jessica M Sidisky,Russell Caratenuto,Daniel Babcock,Daniel Weaver,Sarrah Hussain,Meryem Okumus

doi:10.7554/elife.54932

Abstract

Maintaining synaptic structure and function over time is vital for overall nervous system function and survival. The processes that underly synaptic development are well understood. However, the mechanisms responsible for sustaining synapses throughout the lifespan of an organism are poorly understood. Here, we demonstrate that a previously uncharacterized gene, CG31475, regulates synaptic maintenance in adult Drosophila NMJs. We named CG31475 mayday due to the progressive loss of flight ability and synapse architecture with age. Mayday is functionally homologous to the human protein Cab45, which sorts secretory cargo from the Trans Golgi Network (TGN). We find that Mayday is required to maintain trans-synaptic BMP signaling at adult NMJs in order to sustain proper synaptic structure and function. Finally, we show that mutations in mayday result in the loss of both presynaptic motor neurons as well as postsynaptic muscles, highlighting the importance of maintaining synaptic integrity for cell viability.

Highlights

Synaptic communication is key for proper nervous system function
We examined phosphorylated mothers against DPP (pMad) staining at an early time point and found similar staining between wild type (WT) and myd3PM71 flies (Figure 9A–F), suggesting that bone morphogenic protein (BMP) signaling is not impaired in myd3PM71 mutants at early time points
Our current study describes mayday, a previously uncharacterized gene that plays a role in maintaining synaptic integrity with age by promoting trans-synaptic signaling

Summary

Introduction

Synaptic communication is key for proper nervous system function. Through developmental studies, we have learned that synaptic communication is first established by coordinated events between the presynaptic neuron and the postsynaptic cell (Collins and DiAntonio, 2007; Turrigiano and Nelson, 2004). The DLM NMJs form a tripartite synapse composed of a presynaptic motor neuron, postsynaptic muscle cell, and associated glial cell, that provide the ability to understand synaptic function at the cellular and molecular level (Danjo et al, 2011). The morphogen glass bottom boat (Gbb), the Drosophila ortholog to mammalian BMP7, is secreted in a retrograde manner from the postsynaptic muscle cell to the presynaptic motor neuron (Chen et al, 1998; McCabe et al, 2003; Wharton et al, 1999; Wharton et al, 1991) It is not understood how this pathway could function past development. We demonstrate that this sustained trans-synaptic signaling is required to maintain the viability of both presynaptic motor neurons and postsynaptic muscles

Results

Discussion

Materials and methods

Funding Funder National Institutes of Health