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Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin.

Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine repeat in the HD protein huntingtin. Huntingtin's localization within the cell includes an association with cytoskeletal elements and vesicles. We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner. We now report that HAP1 interacts with cytoskeletal proteins, namely the p150 Glued subunit of dynactin and the pericentriolar protein PCM-1. Structural predictions indicate that both HAP1 and the interacting proteins have a high probability of forming coiled coils. We examined the interaction of HAP1 with p150 Glued . Binding of HAP1 to p150 Glued (amino acids 879-1150) was confirmed in vitro by binding of p150 Glued to a HAP1-GST fusion protein immobilized on glutathione-Sepharose beads. Also, HAP1 co-immunoprecipitated with p150 Glued from brain extracts, indicating that the interaction occurs in vivo . Like HAP1, p150 Glued is highly expressed in neurons in brain and both proteins are enriched in a nerve terminal vesicle-rich fraction. Double label immunofluorescence experiments in NGF-treated PC12 cells using confocal microscopy revealed that HAP1 and p150 Glued partially co-localize. These results suggest that HAP1 might function as an adaptor protein using coiled coils to mediate interactions among cytoskeletal, vesicular and motor proteins. Thus, HAP1 and huntingtin may play a role in vesicle trafficking within the cell and disruption of this function could contribute to the neuronal dysfunction and death seen in HD.

Pubmed ID: 9361024


  • Engelender S
  • Sharp AH
  • Colomer V
  • Tokito MK
  • Lanahan A
  • Worley P
  • Holzbaur EL
  • Ross CA


Human molecular genetics

Publication Data

December 18, 1997

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM48661
  • Agency: NIMH NIH HHS, Id: MH01152
  • Agency: NINDS NIH HHS, Id: NS16375

Mesh Terms

  • Animals
  • Autoantigens
  • Base Sequence
  • Brain Chemistry
  • Carbon-Oxygen Lyases
  • Cell Cycle Proteins
  • Cell Line
  • Chromatography, Affinity
  • Cytoskeleton
  • DNA, Complementary
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Humans
  • Kinesin
  • Macromolecular Substances
  • Microscopy, Confocal
  • Microtubule-Associated Proteins
  • Molecular Sequence Data
  • Nuclear Proteins
  • PC12 Cells
  • Protein Binding
  • Protein Conformation
  • Rats
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae