NLGN3 autism variants have distinct functional impact on synapses and sleep behavior in Drosophila.

Distinct NLGN3 variants linked to autism exhibit different effects on synapse morphology, vesicle dynamics, and sleep behavior in Drosophila models.

• Why it matters: Understanding how specific NLGN3 variants impact neural function can clarify the biological basis of ASD heterogeneity and aid in developing targeted interventions.
• What they did: Researchers generated transgenic Drosophila models with three NLGN3 variants—p.R175W, p.R451C, and p.R597W—and examined their effects on sleep, synaptic architecture, and vesicle dynamics, comparing them to human NLGN3Ref.
• The result: The p.R175W variant showed gain-of-function effects, exacerbating sleep and synapse phenotypes, while p.R451C and p.R597W variants differentially disrupted synaptic development and function, highlighting variant-specific impacts relevant to ASD heterogeneity.