Regulation of synaptic architecture and synaptic vesicle pools by Nervous wreck at Drosophila Type 1b glutamatergic synapses

Abstract

Nervous wreck (Nwk), a protein that is present at Type 1 glutamatergic synapses that contains an SH3 domain and an FCH motif, is a Drosophila homolog of the human srGAP3/MEGAP protein, which is associated with mental retardation. Confocal microscopy revealed that circles in Nwk reticulum enclosed T-shaped active zones (T-AZs) and partially colocalized with synaptic vesicle (SV) markers and both exocytosis and endocytosis components. Results from an electron microscopic (EM) analysis showed that Nwk proteins localized at synaptic edges and in SV pools. Both the synaptic areas and the number of SVs in the readily releasable (RRPs) and reserve (RPs) SV pools in nwk2 were significantly reduced. Synergistic, morphological phenotypes observed from eag1;nwk2 neuromuscular junctions suggested that Nwk may regulate synaptic plasticity differently from activity-dependent Hebbian plasticity. Although the synaptic areas in eag1;nwk2 boutons were not significantly different from those of nwk2, the number of SVs in the RRPs was similar to those of Canton-S. In addition, three-dimensional, high-voltage EM tomographic analysis demonstrated that significantly fewer enlarged SVs were present in nwk2 RRPs. Furthermore, Nwk formed protein complexes with Drosophila Synapsin and Synaptotagmin 1 (DSypt1). Taken together, these findings suggest that Nwk is able to maintain synaptic architecture and both SV size and distribution at T-AZs by interacting with Synapsin and DSypt1.

Comprehensive insights into the impact of bacterial indole-3-acetic acid on sensory preferences in Drosophila melanogaster

“…After ten days of feeding, IAA-fed flies exhibited declined survivability and altered motility (chemotaxis and phototaxis) as compared to respective controls. IAA was found to upregulate the protein nervous wreck (isoform 4), a Drosophila homolog of the human srGAP3/MEGAP protein associated with mental retardation, proposed to control synapse morphology by regulating actin dynamics downstream of growth signals in presynaptic terminals 59 , 60 . However, IAA treatment downregulated msp300, a striated muscle-specific protein exclusively involved in the anchoring of the myonuclei to the core actomyosin fibrillar compartment 61 .…”

Function of Drosophila Synaptotagmins in membrane trafficking at synapses

“…Another potential mechanism would involve SVs being more efficiently recruited from the reserve pool (RP) in the absence of SYT7. The SV protein Synapsin helps maintain the RP by tethering SVs to actin filaments [267][268][269][270][271][272][273][274][275][276][277][278][279] and is known to interact with other peri-AZ proteins to regulate SV cycling [244,280]. As such, SYT7 might modulate a Synapsin-dependent process that controls SV availability.…”

Alteration of unfolded protein responses and autophagy signaling represented the molecular basis underlying saccharin toxicity to Drosophila (Diptera: Drosophilidae)

“…w1118 was used for toxicity tests for saccharin and spinosad, while the FM7c, Kr-Gal4, UAS-GFP, sn + /+ strain was used to examine fat body development. VFs were raised with VF-normal food (VF-Nf, 1 L dH 2 O, 7.7 g agar, 62.4 g dried yeast, 40.8 g corn starch, 84 g glucose, 13 ml molasses, 12.5 ml mold inhibitor; DaeJung Chemicals & Metal Co., Ltd.) (Hur et al, 2018), and SWD was raised with a previously published SWD-Nf diet (1 L dH 2 O, 7.7 g agar, 35.3 g dried yeast, 17.3 g corn starch, 25 g glucose, 25 g fructose, 32 g sucrose, 4.2 ml molasses, 12 ml mold inhibitor) (Nguyen et al, 2016) at 25.0 ± 1.0°C with 60.0 ± 1.0% relative humidity and a light cycle of 16L:8D.…”