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ARRESTIN‐DEPENDENT SUBCELLULAR REDISTRIBUTION OF SIGNALING PROTEINS
Author(s) -
Gurevich Vsevolod V,
Raman Dayanidhi,
Gurevich Eugenia,
Vishnivetskiy Sergey
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a110-b
Subject(s) - microbiology and biotechnology , arrestin , cytoplasm , ubiquitin ligase , biology , subcellular localization , green fluorescent protein , nuclear localization sequence , ubiquitin , hek 293 cells , signal transduction , g protein coupled receptor , receptor , biochemistry , gene
Arrestins bind active phosphorylated G protein‐coupled receptors. Receptor‐bound arrestins interact with numerous proteins, redirecting the signaling to G protein‐independent pathways. Arrestins also have nuclear localization and nuclear exclusion signal and shuttle between the nucleus and the cytoplasm. In neurons endogenous visual and arrestin3 are localized in the cytoplasm, whereas the distribution of arrestin2 varies in different types of cells. Constitutively shuttling proteins often redistribute their interaction partners between the two compartments. We took advantage of the nucleoplasmic shuttling of free arrestins and used “nuclear exclusion assay” to study their interactions with two proteins involved in “life‐and‐death” decisions in the cell, kinase JNK3 and ubiquitin ligase Mdm2. In HEK‐293 cells GFP‐JNK3 and GFP‐Mdm2 predominantly localize to the nucleus, whereas visual arrestin, arrestin2(Q394L) mutant with engineered NES, and arrestin3 localize exclusively to the cytoplasm. Co‐expression of either of these arrestins relocalized both GFP‐JNK3 and GFP‐Mdm2 from the nucleus to the cytoplasm, indicating that free arrestins interact with JNK3 and Mdm2. Robust interaction of free arrestins in their basal conformation (which is usually considered inactive, as opposed to the active receptor‐bound state) with JNK3 and Mdm2 and their ability to regulate subcellular localization of these proteins may play an important role in the survival of photoreceptors and other neurons, as well as in retinal and neuronal degeneration. NIH grants EY11500, GM63097, NS45117