Premium
Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking
Author(s) -
Metzler Martina,
Li Bo,
Gan Lu,
Georgiou John,
Gutekunst ClaireAnne,
Wang Yushan,
Torre Enrique,
Devon Rebecca S.,
Oh Rosemary,
LegendreGuillemin Valerie,
Rich Mark,
Alvarez Christine,
Gertsenstein Marina,
McPherson Peter S.,
Nagy Andras,
Wang Yu Tian,
Roder John C.,
Raymond Lynn A.,
Hayden Michael R.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg334
Subject(s) - ampa receptor , endocytic cycle , biology , clathrin , microbiology and biotechnology , endocytosis , internalization , dynein , dynamin , receptor , glutamate receptor , microtubule , biochemistry
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.