Thesis presented on May 04, 2017
Abstract: Integral proteins of the plasma membrane play a major role in the detection of environmental cues and in the adaptation of cells to variations of their environment. Regulatory mechanisms modulate their presence at the cell surface and control the signaling cascades activated in response to their stimulation. In this context, members of the arrestin revealed to be key regulators, since the discovery of β- and visual arrestins and their well-described role in the regulation of G-protein coupled receptors in complex organisms, and the more recent identification of arrestin-related proteins, present from mammals to protists and sharing functions in membrane cargo trafficking.
This work aims at the functional characterization of two arrestin-related proteins of the social amoeba
Dictyostelium discoideum, the AdcB and AdcC proteins. These two members of the arrestin clan share a similar multimodular organization, specific to Dictyostelids, with a putative N-terminal calcium-binding type C2 domain and two C-terminal SAM domains surrounding the arrestin module. We showed that the C2 domain confers calcium-dependent binding properties to anionic lipids
in vitro and that the SAM domains allow the self-association and hetero-interaction of the two proteins in complexes of high molecular weight. Despite these similarities, AdcB and AdcC harbor a distinct behavior
in vivo as only AdcC translocates to the plasma membrane in response to an intracellular calcium rise triggered by the chemoattractants acid folic and cAMP or extracellular calcium. In parallel, a phenotypic characterization of
adcB and
adcC single or double null mutants and a search for partners were conducted, that open new avenues for future research on these adaptor proteins.
Key words: Arrestins,
Dictyostelium discoideum, C2 domain, SAM motif, calcium signaling, oligomerization
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