Neurexin–Neuroligin 1 regulates synaptic morphology and functions via the WAVE regulatory complex in Drosophila neuromuscular junction

Guanglin Xing,Menglong Rui,Moyi Li,Yichen Sun,Huihui Lv,Junhai Han,Yan Zhuang,Wei Xie,Zhengping Jia

doi:10.7554/elife.30457

Guanglin Xing, Menglong Rui + Show 7 more

Open Access

https://doi.org/10.7554/elife.30457

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Journal: eLife	Publication Date: Mar 14, 2018
Citations: 42	License type: CC BY 4.0

Affiliation: Southeast University, Nantong University, SickKids Foundation

Abstract

Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of neuroligin functions remain unclear. We found that Drosophila Neuroligin 1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence. That interaction is required to recruit WRC to the postsynaptic membrane to promote F-actin assembly. Furthermore, the interaction between DNlg1 and the WRC is essential for DNlg1 to rescue the morphological and electrophysiological defects in dnlg1 mutants. Our results reveal a novel mechanism by which the DNrx-DNlg1 trans-synaptic interaction coordinates structural and functional properties at the neuromuscular junction.

Highlights

Synapses are fundamental components of neural circuits that are essential for normal brain function
We find that mutations in dnlg1, dnlg2, and dnrx each resulted in a dramatic reduction in the amount of actin filaments (F-actin)
When we expressed Drosophila Neuroligin 1 (DNlg1)-EGFP with the muscle-specific Gal4 driver (Mef2-Gal4) in a wild type (WT) background, we found marked F-actin staining at type II boutons that was similar to that observed at type I boutons (Figure 7B,E and G)

Summary

Introduction

Synapses are fundamental components of neural circuits that are essential for normal brain function. The current data from both mammals and flies strongly support the critical involvement of neuroligins in synaptic function and the maturation of the postsynaptic apparatus (Banovic et al, 2010; Chubykin et al, 2007; Poulopoulos et al, 2009; Sun et al, 2011; Varoqueaux et al, 2006; Xing et al, 2014; Zhang et al, 2017) It is still not elucidated how neuroligins regulate those processes. Actin is a key cytoskeletal component that plays a central role in many cellular processes, including cell morphology, motility, and vesicle trafficking (Kaksonen et al, 2006; Le Clainche and Carlier, 2008) It is well known as a critical factor for synaptic formation and function. This study unravels a fundamental mechanism how certain synaptic adhesion molecules regulate synaptic formation and function

Results

Discussion

Materials and methods