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

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

URL: http://www.ncbi.nlm.nih.gov/pubmed/12839988
DOI: 10.1093/emboj/cdg334

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: http://repository.cshl.edu/id/eprint/30967

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