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

Abstract

Arrestins are key adaptor proteins that control the fate of cell-surface membrane proteins and modulate downstream signaling cascades. The 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 an increase in cytosolic calcium by transiently translocating 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 binding to anionic lipids in a calcium-dependent manner and auto-assembly as large homo-oligomers. AdcB can interact with AdcC; however, its intracellular localization is insensitive to calcium. Therefore, despite their high degree of homology and common characteristics, AdcB and AdcC are likely to fulfill distinct functions in amoebae.

From environmental sensing to developmental control: cognitive evolution in dictyostelid social amoebas

“…In addition to these responses which require the G-protein G2, binding of cAMP to cAR1 also triggers G-protein independent responses, such as activation of the protein kinase ERK2, transient influx of Ca 2+ , and phosphorylation of cAR1, which recruits the arrestin AdcC to the plasma membrane, where, activated by Ca 2+ , AdcC causes internalization and degradation of cAR1 as well as inhibition of ERK2 [13,14]. Ca 2+ also inhibits the synthesis of cGMP, a small molecule required for myosinII activation [15].…”