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

Lauriane Mas,Adeline Cieren,Christian Delphin,Agnès Journet,Laurence Aubry

doi:10.1242/jcs.207951

Abstract

Arrestins are key adaptor proteins that control the fate of cell-surface membrane proteins and modulate downstream signaling cascades. The 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 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 in vitro 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.

Highlights

In their environment, cells are constantly subjected to a variety of stimuli that orient their behavior and/or fate in terms of motility, growth and differentiation
A direct role for calcium in AdcC targeting to the plasma membrane Arrestin proteins respond to a variety of external signals, among which a large panel of G-protein-coupled receptors (GPCRs) ligands
Cytosolic in resting conditions, these adaptor proteins translocate to their GPCR targets at the plasma membrane upon receptor ligand activation, and modulate their fate and associated signaling

Summary

Introduction

Cells are constantly subjected to a variety of stimuli that orient their behavior and/or fate in terms of motility, growth and differentiation. Β-arrestins play a central role in the regulation of GPCRs and associated signaling by impeding their coupling to heterotrimeric G proteins, modulating the activation of downstream effectors and controlling GPCR presence at the cell surface (Kendall and Luttrell, 2009; Gurevich and Gurevich, 2015; Tian et al, 2014; DeWire et al, 2007) These scaffolding proteins consist in a double crescent-shaped β-sandwich (arrestin N and C domains) that recognizes the receptor, and a short C-terminal tail The regulation of membrane cargo trafficking appears to be an evolutionarily conserved function of the arrestin clan, and the repertoire of known arrestin membrane targets includes GPCRs, single-membrane span receptors, integrins, channels and transporters, as illustrated in mammals and yeast (Becuwe et al, 2012a; Kang et al, 2014; Kovacs et al, 2009; Lefkowitz et al, 2006; Lin et al, 2008)

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