Calcium influx mediates the chemoattractant-induced translocation of the arrestin-related protein AdcC in Dictyostelium .

Arrestins are key adaptor proteins that control the fate of cell-surface membrane proteins and modulate downstream signaling cascades. Dictyostelium discoideum genome encodes six arrestin-related proteins, harboring additional modules besides the arrestin domain. Here, we studied AdcB and AdcC, two homologs that contain C2 and SAM-domains. We showed that AdcC, in contrast to AdcB, responds to various stimuli (such as the chemoattractants cAMP and folate) known to induce a cytosolic calcium rise by a transient translocation to the plasma membrane and that calcium is a direct regulator of AdcC localization. This response requires the calcium-dependent membrane targeting C2 domain and the double SAM domain involved in AdcC oligomerization, revealing a mode of membrane targeting and regulation unique among members of the arrestin clan. AdcB shares several biochemical properties with AdcC including in vitro binding to anionic lipids in a calcium-dependent manner and auto-assembly as large homo-oligomers. AdcB can interact with AdcC; still its intracellular localization is insensitive to calcium. Despite their high degree of homology and common characteristics, AdcB and AdcC are therefore likely to fulfill distinct functions in amoeba.