Metzler, M., Li, B., Gan, L., Georgiou, J., Gutekunst, C. A., Wang, Y., Torre, E., Devon, R. S., Oh, R., Legendre-Guillemin, V., Rich, M., Alvarez, C., Gertsenstein, M., McPherson, P. S., Nagy, A., Wang, Y. T., Roder, J. C., Raymond, L. A., Hayden, M. R. (July 2003) Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking. Embo Journal, 22 (13). pp. 3254-66. ISSN 0261-4189 (Print)0261-4189
Abstract
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | 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 |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > AMPA receptor diseases & disorders neurobiology |
| CSHL Authors: | |
| Communities: | CSHL labs > Li lab |
| Depositing User: | Matt Covey |
| Date: | 1 July 2003 |
| Date Deposited: | 12 Dec 2014 15:50 |
| Last Modified: | 12 Dec 2014 15:50 |
| PMCID: | PMC165658 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30967 |
Actions (login required)
 |
Administrator's edit/view item |