Abstract |
Paroxysmal nonkinesigenic dyskinesia (PNKD) is an autosomal dominant episodic movement disorder precipitated by coffee, alcohol, and stress. We previously identified the causative gene but the function of the encoded protein remains unknown. We also generated a PNKD mouse model that revealed dysregulated dopamine signaling in vivo. Here, we show that PNKD interacts with synaptic active zone proteins Rab3-interacting molecule ( RIM)1 and RIM2, localizes to synapses, and modulates neurotransmitter release. Overexpressed PNKD protein suppresses release, and mutant PNKD protein is less effective than wild-type at inhibiting exocytosis. In PNKD KO mice, RIM1/2 protein levels are reduced and synaptic strength is impaired. Thus, PNKD is a novel synaptic protein with a regulatory role in neurotransmitter release.
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Authors | Yiguo Shen, Woo-Ping Ge, Yulong Li, Arisa Hirano, Hsien-Yang Lee, Astrid Rohlmann, Markus Missler, Richard W Tsien, Lily Yeh Jan, Ying-Hui Fu, Louis J Ptáček |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 112
Issue 10
Pg. 2935-41
(Mar 10 2015)
ISSN: 1091-6490 [Electronic] United States |
PMID | 25730884
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP-Binding Cassette Transporters
- Abca4 protein, mouse
- Muscle Proteins
- myofibrillogenesis regulator-1, mouse
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Topics |
- ATP-Binding Cassette Transporters
(metabolism)
- Animals
- Chorea
(metabolism)
- Exocytosis
(physiology)
- Mice
- Mice, Knockout
- Muscle Proteins
(genetics, metabolism, physiology)
- Protein Binding
- Synaptic Vesicles
(metabolism)
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