Hippocalcin Functions as a Calcium Sensor in Hippocampal LTD

Summary

It is not fully understood how NMDAR-dependent LTD causes Ca²⁺-dependent endocytosis of AMPARs. Here we show that the neuronal Ca²⁺ sensor hippocalcin binds the β2-adaptin subunit of the AP2 adaptor complex and that along with GluR2 these coimmunoprecipitate in a Ca²⁺-sensitive manner. Infusion of a truncated mutant of hippocalcin (HIP_2-72) that lacks the Ca²⁺ binding domains prevents synaptically evoked LTD but has no effect on LTP. These data indicate that the AP2-hippocalcin complex acts as a Ca²⁺ sensor that couples NMDAR-dependent activation to regulated endocytosis of AMPARs during LTD.