Title: Presynaptic pore-forming protein Brinp2 controls the eEf2 pathway and hippocampal long-term plasticity in an age dependent manner
Pore forming proteins (PFPs) are a large class of proteins which are generally secreted by pathogens or immune systems to inflict membrane damage. Neuron-specific protein Brinp2 belongs to the PFP family and has been associated with neurodegenerative disorders including Alzheimer’s Disease and Parkinson’s Disease, but the function of this putative PFP in the brain is unknown. We find that Brinp2 exhibits lipid binding and multimerization characteristics typically observed for PFPs. In neurons, Brinp2 localizes to a subpopulation of spontaneously released presynaptic vesicles and controls exocytosis of specific vesicle pools in vitro. Loss of Brinp2 in vivo results in an age-dependent decline of hippocampal LTP and a shift in phosphorylation of translational regulator eEf2. Together, we propose that spontaneously released presynaptic Brinp2 controls long-term plasticity and the eEf2 pathway in an age-dependent manner.