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Visual and both non-visual arrestins in their "inactive" conformation bind JNK3 and Mdm2 and relocalize them from the

Xiufeng Song1, Dayanidhi Raman1, Eugenia V Gurevich1

  • 1Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232.

The Journal of Biological Chemistry
|June 2, 2006
PubMed

Insights

Free arrestins bind to JNK3 and Mdm2, proteins involved in cell death. This interaction, observed via nucleocytoplasmic shuttling, suggests arrestins may carry these partners upon receptor binding, impacting neuronal survival.

Area of Science:

  • Cellular signaling and protein interactions.
  • Molecular mechanisms of G protein-coupled receptor (GPCR) regulation.
  • Neurobiology and neuronal cell death pathways.

Background:

  • Arrestins bind activated GPCRs, terminating signaling and interacting with diverse partners.
  • Arrestins shuttle between the nucleus and cytoplasm, potentially influencing cellular localization of interacting proteins.
  • Understanding arrestin interactions is crucial for comprehending neuronal survival and degeneration.

Purpose of the Study:

  • To investigate the interaction between free arrestins and key proteins involved in cell life-and-death decisions: JNK3 and Mdm2.
  • To determine if arrestins can alter the subcellular localization of JNK3 and Mdm2.
  • To elucidate the role of arrestin conformation in these interactions.

Main Methods:

  • Utilized a "nuclear exclusion assay" in human embryonic kidney 293 cells.
  • Coexpressed arrestins (wild-type and mutants) with green fluorescent protein (GFP)-tagged JNK3 and GFP-Mdm2.
  • Observed subcellular localization changes using fluorescence microscopy.

Main Results:

  • GFP-JNK3 and GFP-Mdm2 predominantly localize to the nucleus.
  • Coexpression of arrestins caused a cytoplasmic redistribution of both GFP-JNK3 and GFP-Mdm2.
  • Arrestin mutants in the basal conformation were most effective in causing this redistribution.

Conclusions:

  • Free arrestins interact with JNK3 and Mdm2 in their basal state, suggesting they may be "preloaded" with these partners.
  • Arrestins regulate the subcellular localization of JNK3 and Mdm2.
  • These interactions may be critical for photoreceptor and neuronal survival and in preventing retinal and neuronal degeneration.

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