Molecular mechanism of Ca^<2+> channel protein complexes at presynapse.

• Project/Area Number: 20700334
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kyoto University
• Principal Investigator: KIYONAKA Shigeki Kyoto University, 大学院・工学研究科, 助教 (90422980)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: シナプス / カルシウムチャネル / RIM / 神経伝達物質放出 / RIM1 / 神経伝逹物質放出

Research Abstract

In presynapse, vesicles docking in close vicinity to voltage dependent Ca^<2+> channels (VDCCs) is essential for the control of neurotransmitter release triggered by depolarization-induced Ca^<2+> influx. We have recently reported that VDCC β-subunits physically interact with the presynaptic active zone scaffolding protein RIM1. This interaction cooperates with RIM1-Rab3 interaction to support neurotransmitter exocytosis by anchoring vesicles in the vicinity of VDCCs and by maintaining depolarization-triggered Ca^<2+> influx as a result of marked inhibition of voltage-dependent inactivation of VDCCs. In this research, we demonstrate that other RIM proteins (RIM2-4) also exert prominent suppression on VDCC inactivation via direct binding to β-subunits to enhance neurotransmitter release.

Research Products

• [Journal Article] Involvement of Ca2+ channel synprint site in synaptic vesicle endocytosis. (2010)
  • Author(s): Watanabe H, Yamashita T, Saitoh N, Kiyonaka S, Iwamatsu A, Campbell KP, Mori Y, Takahashi T
  • Journal Title: J. Neurosci 30 Pages: 655-660
• [Journal Article] Ca2+ influx and protein scaffolding via TRPC3 sustain PKCβand ERK activation in B cells. (2010)
  • Author(s): Numaga T, Nishida M, Kiyonaka S, Kato K, Katano M, Mori E, Kurosaki T, Inoue R, Hikida M, Putney Jr JW, Mori Y
  • Journal Title: J. Cell Sci. 123 Pages: 927-938
• [Journal Article] Ca^<2+> influx and protein scaffolding via TRPC3 sustain PKCβ and ERK activation in B cells. (2010)
  • Author(s): Numaga T, Nishida M, Kiyonaka S, (他7名)
  • Journal Title: J.Cell Sci. 123 Pages: 927-938
  • Peer Reviewed
• [Journal Article] A pathogenic C-terminus-truncated polycystin-2 mutant enhances receptor-activated Ca2+ entry via association with TRPC3 and TRPC7. (2009)
  • Author(s): Miyagi K, Kiyonaka S (co-first), Yamada K, Miki T, Mori E, Kato K, Numata T, Sawaguchi Y, Numaga T, Kimura T, Kanai Y, Kawano M, Wakamori M, Nomura H, Koni I, Yamagishi M, Mori Y
  • Journal Title: J. Biol. Chem. 284 Pages: 34400-34412
  • NAID: 120006334914
• [Journal Article] Molecular characterization of flubendiamide sensitivity in lepidopterous ryanodine receptor Ca2+ release channel. (2009)
  • Author(s): Kato K, Kiyonaka S, Sawaguchi Y, Tohnishi M, Masaki T, Yasokawa N, Mizuno Y, Mori E, Inoue K, Hamachi I, Takeshima H, Mori Y
  • Journal Title: Biochemistry 48 Pages: 10342-10352
• [Journal Article] Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound. (2009)
  • Author(s): Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T, Ishii M, Takemoto H, Ojida A, Watanabe K, Uemura A, Kurose H, Morii T, Kobayashi T, Sato Y, Sato C, Hamachi I, Mori Y
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 5740-5745
• [Journal Article] Ca2+-dependent induction of TRPM2 currents in hippocampal neurons. (2009)
  • Author(s): Olah ME, Jackson MF, Li H, Perez Y, Sun HS, Kiyonaka S, Mori Y, Tymianski M, Macdonald JF
  • Journal Title: J. Physiol. 587 Pages: 965-979
• [Journal Article] A pathogenic C-terminus-truncated polycystin-2 mutant enhances receptor-activated Ca^<2+> entry via association with TRPC3 and TRPC7. (2009)
  • Author(s): Miyagi K, Kiyonaka S, (他15名)
  • Journal Title: J.Biol.Chem. 284 Pages: 34400-34412
  • NAID: 120006334914
  • Peer Reviewed
• [Journal Article] Molecular characterization of flubendiamide sensitivity in lepidopterous ryanodine receptor Ca^<2+> release channel. (2009)
  • Author(s): Kato K, Kiyonaka S, (他10名)
  • Journal Title: Biochemistry 48 Pages: 10342-10352
  • Peer Reviewed
• [Journal Article] Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound (2009)
  • Author(s): Kiyonaka S, (他20名)
  • Journal Title: Proc. Nat1. Acad. Sci. USA 106 Pages: 5740-5745
  • Peer Reviewed
• [Journal Article] Changes in temperature preferences and energy homeostasis in dystroglycan mutants (2009)
  • Author(s): Takeuchi K, (他6名), Kiyonaka S, (他3名)
  • Journal Title: Science 323 Pages: 1740-1743
  • Peer Reviewed
• [Journal Article] A CACNB4 mutation shows that altered Ca(v)2. 1 function may be a genetic modifier of severe myoclonic epilepsy in infancy. (2008)
  • Author(s): Ohmori I, Ouchida M, Miki T, Mimaki N, Kiyonaka S, Nishiki T, Tomizawa K, Mori Y, Matsui H
  • Journal Title: Neurobiol. Dis. 32 Pages: 349-354
• [Journal Article] Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators. (2008)
  • Author(s): Takahashi N, Mizuno Y, Kozai D, Yamamoto S, Kiyonaka S, Shibata T, Uchida K, Mori Y
  • Journal Title: Channels 2 Pages: 287-298
• [Journal Article] TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. (2008)
  • Author(s): Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y
  • Journal Title: Nature Med. 14 Pages: 738-747
• [Journal Article] TRPM2-mediated Ca^<2+> influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration (2008)
  • Author(s): Yamamoto S, Shimizu S, KiyonakaS, (他14名)
  • Journal Title: Nature Med. 14 Pages: 738-747
  • Peer Reviewed
• [Journal Article] RIMγisoforms lacking the Rab3-binding domain induce long-lasting currents but block neurotransmitter vesicle-anchoring in voltage-dependent P/Q-type Ca2+ channels.
  • Author(s): Uriu Y, Kiyonaka S, Miki T, Yagi M, Akiyama S, Mori E, Nakao A, Beedle AM, Campbell KP, Wakamori M, Mori Y
  • Journal Title: J. Biol. Chem. (in press)
• [Presentation] 多発性嚢胞腎原因遺伝子ポリシスチン2変異体はTRPC3と複合体を形成し受容体活性化型カルシウム流入を増加させる (2010)
  • Author(s): 清中茂樹, 宮城恭子, 山田和徳, 三木崇史, 森恵美子, 加藤賢太, 沼田朋大, 澤口諭一, 木村徹, 金井好克, 森泰生
  • Organizer: 第83回日本薬理学会大会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2010-03-17
• [Presentation] 多発性嚢胞腎原因遺伝子ポリシスチン2変異体はTRPC3と複合体を形成し受容体活性化型カルシウム流入を増加させる (2010)
  • Author(s): 清中茂樹, (他10名)
  • Organizer: 第83回 日本薬理学会年会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-03-17
• [Presentation] Acetylcholine secretion (% of total content)森泰生、フルベンジアミドによるチョウ目リアノジン受容体カルシウム放出チャネル選択的活性化機構の解明 (2009)
  • Author(s): 加藤賢太, 清中茂樹, 澤口諭一, 遠西正範, 正木隆男, 八十川伯朗, 水野雄介, 森恵美子, 井上圭亮, 浜地格, 竹島浩
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2009-10-24
• [Presentation] 新規TRPC3チャネル阻害剤の開発及び作用機序の解明 (2009)
  • Author(s): 清中茂樹, 加藤賢太, 西田基宏, 澤口諭一, 沼田朋大, 佐藤主税, 浜地格, 森泰生
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2009-10-24
• [Presentation] 新規Ca2+チャネル阻害剤の作用機構解明およびその応用 (2009)
  • Author(s): 清中茂樹, 森泰生
  • Organizer: バイオテクノロジー部会シンポジウム
  • Place of Presentation: 福岡県福岡市
  • Year and Date: 2009-09-14
• [Presentation] RIMファミリータンパク質による電位依存性カルシウムチャネルの機能修飾 (2008)
  • Author(s): 瓜生幸嗣, 若森実, 秋山智志, 山崎浩史, 三木崇史, 清中茂樹, 森恵美子, 森泰生
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2008-12-09
• [Presentation] Functional impact of RIM family sharing C2B domain on gating of voltage-dependent Ca2+ channels (2008)
  • Author(s): Takafumi Miki, Yoshitsugu Uriu, Shigeki Kiyonaka, Yasuo Mori
  • Place of Presentation: Washington DC USA
  • Year and Date: 2008-11-17
• [Presentation] RIM1 confers sutained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels (2008)
  • Author(s): Shigeki Kiyonaka, Yasuo Mori
  • Organizer: FASEB SUMMER RESEARCH CONFERENCES
  • Place of Presentation: Colorado USA
• [Remarks]
  • URL: http://www.sbchem.kyoto-u.ac.jp/mori-lab/