Munc13-1は,グルタマタージックシナプスベジクルの融合能力に不可欠です
I Augustin1, C Rosenmund, T C Südhof
1Max-Planck-Institut für Experimentelle Medizin, AG Molekulare Neurobiologie, Göttingen, Bundesrepublik Deutschland.
Nature
|August 10, 1999
まとめ
Munc13-1はニューロンのシナプス胞の成熟に不可欠です. その欠如は神経伝達物質の放出を停止しますが,いくつかのシナプスとGABAニューロンは影響を受けず,多様な成熟経路を明らかにします.
科学分野:
- 神経科学は神経科学である.
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- 神経伝達物質の放出は,カルシウムによって誘発されるシナプス胞の融合に依存する.
- 前シナプス部位にドッキングする前に,核融合に適した状態への膀の成熟は不可欠です.
研究 の 目的:
- シナプスの成熟に不可欠なタンパク質を特定する.
- シナプスのサイクルと神経伝達物質の放出におけるMunc13-1の役割を調査する.
主な方法:
- Munc13-1ノックアウトマウスを用いて,グルタマタージックヒポカンパニューロンを研究した.
- シナプスの超構造と神経伝達物質の放出メカニズムを調べた.
- Munc13-1欠乏シナプスの放出に対するアルファ-ラトトキシンの効果を調査した.
主要な成果:
- Munc13-1欠乏ニューロンは正常なシナプスを形成するが,膀の成熟が停止している.
- Munc13-1の喪失は,アクションポテンシャル,カルシウムイオノフォール,またはサクロース誘発のトランスミッター放出を妨げます.
- アルファ-ラトロトキシンはMunc13-1の要求を回避し,代替的な放出経路を示しています.
結論:
- Munc13-1はシナプスの成熟と神経伝達物質の放出に不可欠です.
- 神経細胞には,複数のトランスミッター特異のシナプスの成熟経路が存在します.
- GABAergicニューロンとグルタマタージックシナプスのサブセットは,Munc13-1-独立した成熟プロセスを利用します.
関連する概念動画
01:32Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
01:33Coat Assembly and GTPases
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
01:43SNAREs and Membrane Fusion
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
01:29Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
01:10Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.