Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2935-2941
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number10
DOIs
StatePublished - Mar 10 2015

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rab3 GTP-Binding Proteins
Chorea
Synaptic Vesicles
Exocytosis
Proteins
Neurotransmitter Agents
Coffee
Movement Disorders
Paroxysmal nonkinesigenic dyskinesia
Synapses
Dopamine
Alcohols

Keywords

  • Dyskinesia
  • Exocytosis
  • Neurological disease
  • Paroxysmal

ASJC Scopus subject areas

  • General

Cite this

Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis. / Shen, Yiguo; Ge, Woo Ping; Li, Yulong; Hirano, Arisa; Lee, Hsien Yang; Rohlmann, Astrid; Missler, Markus; Tsien, Richard W.; Jan, Lily Yeh; Fu, Ying Hui; Ptáček, Louis J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 10, 10.03.2015, p. 2935-2941.

Research output: Contribution to journalArticle

Shen, Yiguo ; Ge, Woo Ping ; Li, Yulong ; Hirano, Arisa ; Lee, Hsien Yang ; Rohlmann, Astrid ; Missler, Markus ; Tsien, Richard W. ; Jan, Lily Yeh ; Fu, Ying Hui ; Ptáček, Louis J. / Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 10. pp. 2935-2941.
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AU - Lee, Hsien Yang

AU - Rohlmann, Astrid

AU - Missler, Markus

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