Mice lacking an adaptor protein suffer more seizures.

The AP-3 adaptor protein exists in two forms, A and B. Loss of the ubiquitously expressed AP-3A complex leads to widespread problems in lysosome functions. Now, on page 293, Nakatsu et al. show that loss of neuronal-specific AP-3B function causes defects in hippocampal function in mice, increases the magnitude of long-term potentiation, and makes the animals susceptible to seizures.

The team generated mice lacking the 3B-specific subunit μ3B. The animals had no gross morphological brain defects, but were prone to spontaneous and triggered seizures. At hippocampal synapses the number and size of synaptic vesicles was reduced, although baseline release of the neurotransmitters GABA and glutamate were normal. However upon neural stimulation, the mutants released less GABA, the inhibitory neurotransmitter, than did wild-type animals. Nakatsu et al. found that synaptic vesicles had reduced integration of the GABA-specific transporter VGAT but normal levels of the glutamate transporter VGLUT.

The team hypothesizes that AP-3B is critical for the biogenesis of a subset of synaptic vesicles in hippocampal neurons and that VGAT may be a specific cargo for AP-3B. Also, because there is more glutamate than GABA available in the system, a reduction in glutamate vesicle biogenesis may be compensated for by efficient vesicle recycling at the plasma membrane.