Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking
| Autor: | Yu Tian Wang, Michael R. Hayden, Andras Nagy, Martina Metzler, Claire-Anne Gutekunst, Marina Gertsenstein, Rosemary Oh, Bo Li, John C. Roder, Peter S. McPherson, Lu Gan, Christine M. Alvarez, Yushan Wang, Valerie Legendre-Guillemin, Mark M. Rich, John Georgiou, Enrique Torre, Rebecca S. Devon, Lynn A. Raymond |
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| Rok vydání: | 2003 |
| Předmět: |
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Endocytic cycle Fluorescent Antibody Technique AMPA receptor Endocytosis Clathrin General Biochemistry Genetics and Molecular Biology Mice Pregnancy Animals Receptors AMPA Internalization Receptor alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Molecular Biology media_common General Immunology and Microbiology biology General Neuroscience Glutamate receptor Brain Articles Huntingtin-interacting protein 1 Cell biology DNA-Binding Proteins Protein Transport Phenotype Spinal Cord nervous system Immunology biology.protein Colorimetry Female Carrier Proteins |
| Zdroj: | ResearcherID |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/cdg334 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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