The N-ethylmaleimide-sensitive factor and dysbindin interact to modulate synaptic plasticity

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Dysbindin is a schizophrenia susceptibility factor and a component of BLOC-1, crucial for organelle biogenesis and neuronal function.
• The downstream interactome of dysbindin/BLOC-1 is not fully understood, hindering insights into neurodevelopmental disorders.

Purpose of the Study:

• To identify proteins whose levels are affected by dysbindin/BLOC-1 loss of function.
• To investigate the role of NSF in dysbindin/BLOC-1-dependent synaptic plasticity.

Main Methods:

• Proteome-wide search for proteins sensitive to dysbindin/BLOC-1 deficiency.
• Co-immunoprecipitation assays to assess protein interactions.
• Analysis of synaptic homeostatic plasticity in Drosophila models with genetic manipulations.

Main Results:

• Components of the vesicle fusion machinery, including NSF, were downregulated in dysbindin/BLOC-1 deficient cells.
• Dysbindin/BLOC-1 and NSF physically interact and colocalize at synapses.
• Presynaptic expression of dysbindin or NSF rescued synaptic plasticity defects in dysbindin mutants.

Conclusions:

• Dysbindin/BLOC-1 deficiency alters the cellular levels of vesicle fusion proteins.
• Dysbindin and NSF are functionally linked in regulating synaptic plasticity.
• These findings illuminate a molecular mechanism underlying synaptic dysfunction in neurodevelopmental disorders.