Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking

EMBO J. 2003 Jul 1;22(13):3254-66. doi: 10.1093/emboj/cdg334.


Huntingtin interacting protein 1 (HIP1) is a recently identified component of clathrin-coated vesicles that plays a role in clathrin-mediated endocytosis. To explore the normal function of HIP1 in vivo, we created mice with targeted mutation in the HIP1 gene (HIP1(-/-)). HIP1(-/-) mice develop a neurological phenotype by 3 months of age manifest with a failure to thrive, tremor and a gait ataxia secondary to a rigid thoracolumbar kyphosis accompanied by decreased assembly of endocytic protein complexes on liposomal membranes. In primary hippocampal neurons, HIP1 colocalizes with GluR1-containing AMPA receptors and becomes concentrated in cell bodies following AMPA stimulation. Moreover, a profound dose-dependent defect in clathrin-mediated internalization of GluR1-containing AMPA receptors was observed in neurons from HIP1(-/-) mice. Together, these data provide strong evidence that HIP1 regulates AMPA receptor trafficking in the central nervous system through its function in clathrin-mediated endocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Carrier Proteins / metabolism*
  • Clathrin / metabolism
  • Colorimetry
  • DNA-Binding Proteins*
  • Endocytosis*
  • Female
  • Fluorescent Antibody Technique
  • Mice
  • Phenotype
  • Pregnancy
  • Protein Transport
  • Receptors, AMPA / metabolism*
  • Spinal Cord / metabolism
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Carrier Proteins
  • Clathrin
  • DNA-Binding Proteins
  • Hip1 protein, mouse
  • Receptors, AMPA
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid