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

Juan Rong, Shihua Li, Guoqing Sheng, Meng Wu, Brian Coblitz, Min Li, Haian Fu, Xiao Jiang Li

Research output: Contribution to journalArticle

Abstract

HAP1 (Huntingtin-associated protein 1) consists of two alternately spliced isoforms(HAP1A and HAP1B, which have unique C-terminal sequences) and participates in intracellular trafficking. The C terminus of HAP1A is phosphorylated, and this phosphorylation was found to decrease the association of HAP1A with kinesin light chain, a protein involved in anterograde transport in cells. It remains unclear how this phosphorylation functions to regulate the association of HAP1 with trafficking proteins. Using the yeast two-hybrid system, we found that HAP1 also interacts with 14-3-3 proteins, which are involved in the assembly of protein complexes and the regulation of protein trafficking. The interaction of HAP1 with 14-3-3 is confirmed by their immunoprecipitation and colocalization in mouse brain. Moreover, this interaction is specific to HAP1A and is increased by the phosphorylation of the C terminus of HAP1A. We also found that expression of 14-3-3 decreases the association of HAP1A with kinesin light chain. As a result, there is less HAP1A distributed in neurite tips of PC12 cells that overexpress 14-3-3. Also, overexpression of 14-3-3 reduces the effect of HAP1A in promoting neurite outgrowth of PC12 cells. We propose that the phosphorylation-dependent interaction of HAP1A with 14-3-3 regulates HAP1 function by influencing its association with kinesin light chain and trafficking in neuronal processes.

Original languageEnglish (US)
Pages (from-to)4748-4756
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number7
DOIs
StatePublished - Feb 16 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Rong, J., Li, S., Sheng, G., Wu, M., Coblitz, B., Li, M., Fu, H., & Li, X. J. (2007). 14-3-3 Protein interacts with Huntingtin-associated protein 1 and regulates its trafficking. Journal of Biological Chemistry, 282(7), 4748-4756. https://doi.org/10.1074/jbc.M609057200