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Misfolded Gβ is recruited to cytoplasmic dynein by Nudel for efficient clearance

Yihan Wan1, Zhenye Yang, Jing Guo

  • 1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.

Cell Research
|March 21, 2012
PubMed

Insights

Misfolded Gβ proteins are polyubiquitinated and degraded by the proteasome. Nudel recruits misfolded Gβ to dynein motors for transport to the centrosome, ensuring protein quality control and signaling termination.

Area of Science:

  • Cellular Biology
  • Protein Degradation
  • Signal Transduction

Background:

  • The Gβγ heterodimer is crucial for signal transduction.
  • Gβ protein misfolding requires chaperones and Gγ for proper folding.
  • Cellular mechanisms for disposing of misfolded Gβ (mfGβ) remain unclear.

Purpose of the Study:

  • To elucidate the cellular disposal pathway for misfolded Gβ.
  • To investigate the role of Nudel and dynein in mfGβ degradation.
  • To understand how mfGβ impacts Gβγ signaling.

Main Methods:

  • Proteasome inhibition using MG132 to observe mfGβ sequestration.
  • Assessment of mfGβ polyubiquitination and proteasomal degradation.
  • Co-immunoprecipitation assays to study protein interactions (Gβ, Nudel, dynein).
  • RNA interference (RNAi) to deplete Nudel levels.
  • Analysis of mfGβ half-life and aggresome formation.

Main Results:

  • Misfolded Gβ is polyubiquitinated and degraded by the proteasome.
  • Proteasome inhibition leads to mfGβ sequestration in aggresomes.
  • Nudel directly interacts with both ubiquitinated and unubiquitinated mfGβ.
  • Nudel facilitates the recruitment of mfGβ to dynein motors.
  • Dynein-dependent transport of mfGβ to the centrosome for degradation.
  • Nudel depletion impairs mfGβ degradation and prolongs its half-life.

Conclusions:

  • Cytosolic misfolded Gβ is recruited by Nudel to dynein for transport to the centrosome.
  • This pathway ensures efficient degradation of mfGβ, maintaining protein quality control.
  • The process may also contribute to the termination of Gβγ signaling.

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