Disruption of the Endocytic Protein HIP1 Results in Neurological Deficits and Decreased AMPA Receptor Trafficking

Authors

• Martina Metzler, The University of British Columbia
• Bo Li
• Lu Gan, The University of British Columbia
• John Georgiou, Mount Sinai Hospital
• Claire Anne Gutekunst, Emory University School of Medicine
• Yushan Wang
• Enrique Torre, Emory University School of Medicine
• Rebecca S. Devon, The University of British Columbia
• Rosemary Oh, The University of British Columbia
• Valerie Legendre-Guillemin, McGill University
• Mark M. Rich, Wright State UniversityFollow
• Christine Alvarez, The University of British Columbia
• Marina Gertsenstein, Mount Sinai Hospital
• Peter S. McPhersons, McGill University
• Andras Nagy, Mount Sinai Hospital
• Yu Tian Wang
• John C. Roder, Mount Sinai Hospital
• Lynn A. Raymond
• Michael R. Hayden, The University of British Columbia

Document Type

Article

Publication Date

7-1-2003

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.

Repository Citation

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. M., Alvarez, C., Gertsenstein, M., McPhersons, P. S., Nagy, A., Wang, Y. T., Roder, J. C., Raymond, L. A., & Hayden, M. R. (2003). Disruption of the Endocytic Protein HIP1 Results in Neurological Deficits and Decreased AMPA Receptor Trafficking. EMBO Journal, 22 (13), 3254-3266.
https://corescholar.libraries.wright.edu/cosm_ncbp/26

DOI

10.1093/emboj/cdg334