The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin
Open accessAbstract
The density of GABAA receptors (GABAARs) at synapses regulates brain excitability, and altered inhibition may contribute to Huntington’s disease, which is caused by a polyglutamine repeat in the protein huntingtin. However, the machinery that delivers GABAARs to synapses is unknown. We demonstrate that GABAARs are trafficked to synapses by the kinesin family motor protein 5 (KIF5). We identify the adaptor linking the receptors to KIF5 as the huntingtin associated protein 1 (HAP1). Disrupting the HAP1-KIF5 complex decreases synaptic GABAAR number, and reduces the amplitude of inhibitory postsynaptic currents. When huntingtin is mutated as in Huntington’s disease, GABAAR transport and inhibitory synaptic currents are reduced. Thus, HAP1-KIF5 dependent GABAAR trafficking is a fundamental mechanism controlling the strength of synaptic inhibition in the brain. Its disruption by mutant huntingtin may explain some of the defects in brain information processing occurring in Huntington’s disease, and provides a new molecular target for therapeutic approaches.
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Citations
Cites
Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism
Yuen, E. Y. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1187-05.2005 · Cited by 225
Self-citationSynaptic dysfunction in Huntington's disease: a new perspective
Smith, R., Brundin, P., & Li, J.-Y. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5084-5 · Cited by 166
Cited by
Hirokawa, N., Niwa, S., & Tanaka, Y. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.039 · Cited by 1,138
Axonal transport deficits and neurodegenerative diseases
Millecamps, S., & Julien, J.-P. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3380 · Cited by 755
The Postsynaptic Organization of Synapses
Sheng, M., & Kim, E. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005678 · Cited by 603
GABAA Receptor Trafficking-Mediated Plasticity of Inhibitory Synapses
Luscher, B., Fuchs, T., & Kilpatrick, C. L. (2011) · Neuron · doi:10.1016/j.neuron.2011.03.024 · Cited by 434
Wong, Y. C., & Holzbaur, E. L. F. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1870-13.2014 · Cited by 398
Metadata
- Authors
- Twelvetrees, A. E., Yuen, E. Y., Arancibia-Carcamo, I. L., MacAskill, A. F., Rostaing, P., Lumb, M. J., Humbert, S., Triller, A., Saudou, F., Yan, Z., & Kittler, J. T.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 65
- Issue
- 1
- Pages
- 53-65
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2145510016
- Cited by
- 276
- References
- 2
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Twelvetrees, A. E., Yuen, E. Y., Arancibia-Carcamo, I. L., MacAskill, A. F., Rostaing, P., Lumb, M. J., Humbert, S., Triller, A., Saudou, F., Yan, Z., & Kittler, J. T. (2010). Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin. Neuron. https://doi.org/10.1016/j.neuron.2009.12.007
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