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

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2003 Jul 4

PMID 12839988

Citations 44

Authors

Martina Metzler

Bo Li

Lu Gan

John Georgiou

Claire-Anne Gutekunst

Yushan Wang

Enrique Torre

Rebecca S Devon

Rosemary Oh

Valerie Legendre-Guillemin

Mark Rich

Christine Alvarez

Marina Gertsenstein

Peter S McPherson

Andras Nagy

Yu Tian Wang

John C Roder

Lynn A Raymond

Michael R Hayden

Affiliations

Soon will be listed here.

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.

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References

Li Y, Chin L, Levey A, Li L . Huntingtin-associated protein 1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate and functions in endosomal trafficking. J Biol Chem. 2002; 277(31):28212-21. DOI: 10.1074/jbc.M111612200. View

Burbea M, Dreier L, Dittman J, Grunwald M, Kaplan J . Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C. elegans. Neuron. 2002; 35(1):107-20. DOI: 10.1016/s0896-6273(02)00749-3. View

Mishra S, Keyel P, Hawryluk M, Agostinelli N, Watkins S, Traub L . Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor. EMBO J. 2002; 21(18):4915-26. PMC: 126284. DOI: 10.1093/emboj/cdf487. View

Ford M, Mills I, Peter B, Vallis Y, Praefcke G, Evans P . Curvature of clathrin-coated pits driven by epsin. Nature. 2002; 419(6905):361-6. DOI: 10.1038/nature01020. View

Sheng M, Kim M . Postsynaptic signaling and plasticity mechanisms. Science. 2002; 298(5594):776-80. DOI: 10.1126/science.1075333. View

Lee S, Liu L, Wang Y, Sheng M . Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD. Neuron. 2002; 36(4):661-74. DOI: 10.1016/s0896-6273(02)01024-3. View

Hussain N, Yamabhai M, Bhakar A, Metzler M, Ferguson S, Hayden M . A role for epsin N-terminal homology/AP180 N-terminal homology (ENTH/ANTH) domains in tubulin binding. J Biol Chem. 2003; 278(31):28823-30. DOI: 10.1074/jbc.M300995200. View

Ahle S, Mann A, Eichelsbacher U, Ungewickell E . Structural relationships between clathrin assembly proteins from the Golgi and the plasma membrane. EMBO J. 1988; 7(4):919-29. PMC: 454417. DOI: 10.1002/j.1460-2075.1988.tb02897.x. View

Metzler M, Gertz A, Sarkar M, SCHACHTER H, Schrader J, Marth J . Complex asparagine-linked oligosaccharides are required for morphogenic events during post-implantation development. EMBO J. 1994; 13(9):2056-65. PMC: 395055. DOI: 10.1002/j.1460-2075.1994.tb06480.x. View

10.

DiFiglia M, Sapp E, Chase K, Schwarz C, Meloni A, Young C . Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron. 1995; 14(5):1075-81. DOI: 10.1016/0896-6273(95)90346-1. View

11.

Ohno H, Stewart J, Fournier M, Bosshart H, Rhee I, Miyatake S . Interaction of tyrosine-based sorting signals with clathrin-associated proteins. Science. 1995; 269(5232):1872-5. DOI: 10.1126/science.7569928. View

12.

Li X, Li S, Sharp A, Nucifora Jr F, Schilling G, Lanahan A . A huntingtin-associated protein enriched in brain with implications for pathology. Nature. 1995; 378(6555):398-402. DOI: 10.1038/378398a0. View

13.

Takei K, Mundigl O, Daniell L, De Camilli P . The synaptic vesicle cycle: a single vesicle budding step involving clathrin and dynamin. J Cell Biol. 1996; 133(6):1237-50. PMC: 2120898. DOI: 10.1083/jcb.133.6.1237. View

14.

Wanker E, Rovira C, Scherzinger E, Hasenbank R, Walter S, Tait D . HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system. Hum Mol Genet. 1997; 6(3):487-95. DOI: 10.1093/hmg/6.3.487. View

15.

Gonzalez-Gaitan M, Jackle H . Role of Drosophila alpha-adaptin in presynaptic vesicle recycling. Cell. 1997; 88(6):767-76. DOI: 10.1016/s0092-8674(00)81923-6. View

16.

Kalchman M, Koide H, McCutcheon K, Graham R, Nichol K, Nishiyama K . HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nat Genet. 1997; 16(1):44-53. DOI: 10.1038/ng0597-44. View

17.

Johnston M . Hypoxic and ischemic disorders of infants and children. Lecture for 38th meeting of Japanese Society of Child Neurology, Tokyo, Japan, July 1996. Brain Dev. 1997; 19(4):235-9. DOI: 10.1016/s0387-7604(96)00561-x. View

18.

Li S, Gutekunst C, Hersch S, Li X . Interaction of huntingtin-associated protein with dynactin P150Glued. J Neurosci. 1998; 18(4):1261-9. PMC: 6792727. View

19.

Martin L, Furuta A, Blackstone C . AMPA receptor protein in developing rat brain: glutamate receptor-1 expression and localization change at regional, cellular, and subcellular levels with maturation. Neuroscience. 1998; 83(3):917-28. DOI: 10.1016/s0306-4522(97)00411-9. View

20.

Faber P, Barnes G, Srinidhi J, Chen J, Gusella J, Macdonald M . Huntingtin interacts with a family of WW domain proteins. Hum Mol Genet. 1998; 7(9):1463-74. DOI: 10.1093/hmg/7.9.1463. View