Rab3A and Rab3D control the total granule number and the fraction of granules docked at the plasma membrane in PC12 cells

Rab proteins are Ras-like GTPases that regulate traffic along the secretory or endocytic pathways. Within the Rab family, Rab3 proteins are expressed at high levels in neurons and endocrine cells where they regulate release o f dense core granules and synaptic vesicles. Immunoelectron microscopy show s that Rab3A and Rab3D can coexist on the same granule before and after doc king. Using electron microscopy of transfected PC12 cells, we report that e xpression of wild-type Rab3A (or Rab3D) increases the total number of granu les and the percentage that is docked at the plasma membrane. Mutated Rab3A N135I (or Rab3D N135I) decreases the total granule number and the fraction of granules docked to the plasma membrane. These data show that at least o ne of the functions of Rab3A and Rab3D proteins is to control the number of granules docked at the plasma membrane.