Biochemical Journal Young Investigator Award

Akiko Kobayashi

Akiko Kobayashi graduated from the Graduate School of Pharmaceutical Sciences, the University of Tokyo, and obtained her PhD in March 2006. In her PhD thesis, Akiko focused on the molecular mechanism underlying the regulation of synaptic vesicle (SV) endocytosis that is a critical step in SV recycling. SVs are retrieved by clathrin-mediated endocytosis at nerve terminals. Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] has been implicated in this event by recruiting endocytic machineries such as the AP-2 adaptor complex. Although PI(4,5)P₂ is present in the plasma membrane of the synapse at the resting state of neurons, SV endocytosis is triggered only when neurons are activated. This led Akiko to speculate that a specific pool of PI(4,5)P₂ could be produced in response to synapse activation to induce SV endocytosis. Akiko found that the β2 subunit of the AP-2 complex directly interacts with the C-terminal tail of the dephosphorylated phosphatidylinositol 4-phosphate 5-kinase γ661 (PIP5Kγ661), the major PI(4,5)P₂-producing enzyme in the brain, and that the interaction activates PIP5Kγ661. The interaction was also observed in mouse hippocampal neurons when they were depolarized. Finally, overexpression of the PIP5Kγ661 C-terminal region in hippocampal neurons suppressed depolarization-dependent SV endocytosis. These findings provide evidence that the interaction between PIP5Kγ661 and AP-2 is an absolute requirement for SV endocytosis.