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Pathogenic huntingt...
Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin
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Morfini, Gerardo A (author)
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You, Yi-Mei (author)
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Pollema, Sarah L (author)
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Kaminska, Agnieszka (author)
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Liu, Katherine (author)
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Yoshioka, Katsuji (author)
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- Björkblom, Benny (author)
- Turku Centre for Biotechnology, Åbo Akademi and Turku University, Turku, Finland
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Coffey, Eleanor T (author)
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Bagnato, Carolina (author)
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Han, David (author)
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Huang, Chun-Fang (author)
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Banker, Gary (author)
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Pigino, Gustavo (author)
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Brady, Scott T (author)
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(creator_code:org_t)
- 2009-06-14
- 2009
- English.
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In: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 12:7, s. 864-871
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Selected vulnerability of neurons in Huntington's disease suggests that alterations occur in a cellular process that is particularly critical for neuronal function. Supporting this idea, pathogenic Htt (polyQ-Htt) inhibits fast axonal transport (FAT) in various cellular and animal models of Huntington's disease (mouse and squid), but the molecular basis of this effect remains unknown. We found that polyQ-Htt inhibited FAT through a mechanism involving activation of axonal cJun N-terminal kinase (JNK). Accordingly, we observed increased activation of JNK in vivo in cellular and mouse models of Huntington's disease. Additional experiments indicated that the effects of polyQ-Htt on FAT were mediated by neuron-specific JNK3 and not by ubiquitously expressed JNK1, providing a molecular basis for neuron-specific pathology in Huntington's disease. Mass spectrometry identified a residue in the kinesin-1 motor domain that was phosphorylated by JNK3 and this modification reduced kinesin-1 binding to microtubules. These data identify JNK3 as a critical mediator of polyQ-Htt toxicity and provide a molecular basis for polyQ-Htt–induced inhibition of FAT.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- General Neuroscience
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Morfini, Gerardo ...
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You, Yi-Mei
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Pollema, Sarah L
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Kaminska, Agnies ...
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Liu, Katherine
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Yoshioka, Katsuj ...
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show more...
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Björkblom, Benny
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Coffey, Eleanor ...
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Bagnato, Carolin ...
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Han, David
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Huang, Chun-Fang
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Banker, Gary
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Pigino, Gustavo
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Brady, Scott T
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Nature Neuroscie ...
- By the university
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Umeå University