Hippocalcin Functions as a Calcium Sensor in Hippocampal LTD
It is not fully understood how NMDAR-dependent LTD causes Ca^2^+-dependent endocytosis of AMPARs. Here we show that the neuronal Ca^2^+ sensor hippocalcin binds the @b2-adaptin subunit of the AP2 adaptor complex and that along with GluR2 these coimmunoprecipitate in a Ca^2^+-sensitive manner. Infusion of a truncated mutant of hippocalcin (HIP"2"-"7"2) that lacks the Ca^2^+ binding domains prevents synaptically evoked LTD but has no effect on LTP. These data indicate that the AP2-hippocalcin complex acts as a Ca^2^+ sensor that couples NMDAR-dependent activation to regulated endocytosis of AMPARs during LTD.
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