Back

Arf GAP containing dAsap regulates NMJ organization and synaptic calcium through Arf6-dependent signaling in Drosophila

Mallik, B.; Kushwaha, S.; Bisht, A.; MJ, H.; Frank, C. A.; Kumar, V.

2023-07-02 neuroscience
10.1101/2023.06.30.547304 bioRxiv
Show abstract

Synaptic morphogenesis involves an interplay of multiple signaling pathways and requires membrane remodeling and cytoskeleton dynamics. We identified the BAR-domain protein dAsap (Arf GAP, SH3, Ankyrin repeat, and PH domain) as one of the regulators of synaptic morphogenesis. Loss of dAsap results in decreased bouton numbers, increased inter-bouton diameter, and disrupted microtubule organization at the nerve terminals. Electrophysiological analysis of the mutants revealed a gain in neurotransmission compared to control neuromuscular junctions (NMJs). dAsap mutant NMJs have increased evoked amplitude, increased spontaneous miniature frequency, and significantly fewer synaptic failures in low calcium. Consistent with these observations, dAsap mutants have increased active zone number. Additional pharmacological and genetic manipulations that are known to impair calcium release from stores suppress the dAsap phenotypes. Finally, we show that expressing a GDP-locked form of Arf6 in dAsap mutants restored the NMJ morphological defects, disrupted cytoskeleton, and aberrant neurotransmission. Thus, we propose a model in which dAsap regulates NMJ morphogenesis and synaptic calcium homeostasis through Arf6-dependent neuronal signaling.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.