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Kim, Jae-Ick
Neural Circuit and Neurodegenerative Disease Lab.
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The THO Complex Coordinates Transcripts for Synapse Development and Dopamine Neuron Survival

Author(s)
Maeder, Celine I.Kim, Jae-IckLiang, XingKaganovsky, KonstantinShen, AoLi, QinLi, ZhaoyuWang, SuiXu, X. Z. ShawnLi, Jin BillyXiang, Yang KevinDing, Jun B.Shen, Kang
Issued Date
2018-09
DOI
10.1016/j.cell.2018.07.046
URI
https://scholarworks.unist.ac.kr/handle/201301/24969
Fulltext
https://www.sciencedirect.com/science/article/pii/S0092867418309747?via%3Dihub
Citation
CELL, v.174, no.6, pp.1436 - 1449
Abstract
Synaptic vesicle and active zone proteins are required for synaptogenesis. The molecular mechanisms for coordinated synthesis of these proteins are not understood. Using forward genetic screens, we identified the conserved THO nuclear export complex (THOC) as an important regulator of presynapse development in C. elegans dopaminergic neurons. In THOC mutants, synaptic messenger RNAs are retained in the nucleus, resulting in dramatic decrease of synaptic protein expression, near complete loss of synapses, and compromised dopamine function. CRE binding protein (CREB) interacts with THOC to mark synaptic transcripts for efficient nuclear export. Deletion of Thoc5, a THOC subunit, in mouse dopaminergic neurons causes severe defects in synapse maintenance and subsequent neuronal death in the substantia nigra compacta. These cellular defects lead to abrogated dopamine release, ataxia, and animal death. Together, our results argue that nuclear export mechanisms can select specific mRNAs and be a rate-limiting step for neuronal differentiation and survival.
Publisher
CELL PRESS
ISSN
0092-8674
Keyword
MESSENGER-RNA-EXPORTCAENORHABDITIS-ELEGANSNUCLEOCYTOPLASMIC TRANSPORTNERVOUS-SYSTEMNUCLEAR EXPORTIN-VIVOCREBPROTEINPLASTICITYMOUSE

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