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14-3-3 protein interacts with Huntingtin-associated protein 1 and regulates its trafficking

Juan Rong1, Shihua Li1, Guoqing Sheng1

  • 1Department of Human Genetics and the Emory University School of Medicine, Atlanta, Georgia 30322.

The Journal of Biological Chemistry
|December 15, 2006
PubMed

Insights

Huntingtin-associated protein 1A (HAP1A) phosphorylation regulates its interaction with 14-3-3 proteins. This interaction influences HAP1A

Area of Science:

  • Cell biology
  • Neuroscience
  • Molecular biology

Background:

  • Huntingtin-associated protein 1 (HAP1) is involved in intracellular trafficking.
  • HAP1 has two isoforms, HAP1A and HAP1B, with distinct C-terminal sequences.
  • Phosphorylation of HAP1A's C terminus affects its association with kinesin light chain, crucial for anterograde transport.

Purpose of the Study:

  • To investigate the regulatory mechanism of HAP1 phosphorylation in protein trafficking.
  • To identify novel interacting partners of HAP1.
  • To elucidate the role of 14-3-3 proteins in HAP1-mediated trafficking.

Main Methods:

  • Yeast two-hybrid system to identify HAP1 interacting proteins.
  • Immunoprecipitation and co-localization studies to confirm HAP1-14-3-3 interaction in mouse brain.
  • Neurite outgrowth assays in PC12 cells to assess HAP1 function.

Main Results:

  • HAP1 interacts with 14-3-3 proteins, and this interaction is specific to HAP1A and enhanced by C-terminal phosphorylation.
  • 14-3-3 binding decreases the association of HAP1A with kinesin light chain.
  • Overexpression of 14-3-3 reduces HAP1A at neurite tips and impairs HAP1A-promoted neurite outgrowth.

Conclusions:

  • Phosphorylation-dependent binding of HAP1A to 14-3-3 proteins regulates HAP1A function.
  • This interaction modulates HAP1A's association with kinesin light chain, impacting neuronal trafficking.
  • HAP1A-14-3-3 interaction is a key regulator of HAP1A's role in neuronal processes.

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