Aggregate formation and the impairment of long-term synaptic facilitation by ectopic expression of mutant huntingtin in Aplysia neurons |
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Authors: | Lee Jin-A Lim Chae-Seok Lee Seung-Hee Kim Hyoung Nukina Nobuyuki Kaang Bong-Kiun |
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Institution: | National Research Laboratory, Institute of Molecular Biology and Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea. |
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Abstract: | Huntington's disease (HD) is caused by an expansion of a polyglutamine (polyQ) tract within huntingtin (htt) protein. To examine the cytotoxic effects of polyQ-expanded htt, we overexpressed an enhanced green fluorescent protein (EGFP)-tagged N-terminal fragment of htt with 150 glutamine residues (Nhtt150Q-EGFP) in Aplysia neurons. A combined confocal and electron microscopic study showed that Aplysia neurons expressing Nhtt150Q-EGFP displayed numerous abnormal aggregates (diameter 0.5-5 microm) of filamentous structures, which were formed rapidly (approximately 2 h) but which were sustained for at least 18 days in the cytoplasm. Furthermore, the overexpression of Nhtt150Q-EGFP in sensory cells impaired 5-hydroxytryptamine (5-HT)-induced long-term synaptic facilitation in sensori-motor synapses without affecting basal synaptic strength or short-term facilitation. This study demonstrates the stability of polyQ-based aggregates and their specific effects on long-term synaptic plasticity. |
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Keywords: | aggregation Aplysia huntingtin polyglutamine synaptic facilitation |
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