Protein Kinase C and Calmodulin Serve As Calcium Sensors for Calcium-Stimulated Endocytosis at Synapses

Calcium influx triggers and facilitates endocytosis, which recycles vesicles and thus sustains synaptic transmission. Despite decades of studies, the underlying calcium sensor remained not well understood. Here, we examined two calcium binding proteins, protein kinase C (PKC) and calmodulin. Whether PKC is involved in endocytosis was unclear; whether calmodulin acts as a calcium sensor for endocytosis was neither clear, although calmodulin involvement in endocytosis had been suggested. We generated PKC (alpha or beta-isoform) and calmodulin (calmodulin 2 gene) knock-out mice of either sex and measured endocytosis with capacitance measurements, pHluorin imaging and electron microscopy. We found that these knock-outs inhibited slow (similar to 10-30 s) and rapid (