SNARE蛋白质:一个用于融合,三个用于保持新生的融合孔开放
Lei Shi1, Qing-Tao Shen, Alexander Kiel
1Department of Cell Biology, School of Medicine, Yale University, New Haven, CT 06520, USA.
概括
由可溶性N-乙胺胺敏感因子附着蛋白受体 (SNARE) 复合体形成的新融化的毛孔是神经递质释放的关键. 在突触传输过程中需要多个SNAREpins来有效释放内容,防止孔隙重新密封.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 神经递质释放通过融合孔发生,这些孔通常会膨胀,阻碍了详细的生物化学分析.
- 了解融合孔动态的精确机制对于神经科学和药物开发至关重要.
研究的目的:
- 调查SNARE复合体在融合孔形成和稳定性中的作用.
- 用脂质双层纳米光盘作为模型系统来描述融合孔的特性.
主要方法:
- 利用脂质双层纳米光盘作为融合伙伴来稳定新生的融合孔.
- 采用SNARE (可溶性N-乙烯胺胺敏感因子附着蛋白受体) 复合体来诱导和研究双层融合.
- 研究了SNAREpin静脉测量和VAMP2跨膜域对内容释放的影响.
主要成果:
- 每个纳米盘单个SNARE足以实现最大的双层融合速率.
- 在生理时间尺度上有效释放神经递质需要三种或更多的SNAREpins和原生VAMP2跨膜域.
- 多个SNARE跨膜螺旋的拉链提供了一个辐射力,防止过早的孔隙重新密封.
结论:
- 通过稳定融合孔,多个SNAREpins对于同步的神经递质释放至关重要.
- 这种机制确保在突触传输过程中有效地驱逐内容,克服孔隙扩张.
- 这些发现提供了对调节式外细胞形成的分子机制的洞察.
相关概念视频
SNAREs 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...
Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
Protein Translocation Machinery on the ER Membrane
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Cytoskeletal Accessory Proteins
The cytoskeleton is an essential cell component that plays several structural and functional roles. However, the filaments that make up the cytoskeleton cannot function independently and depend on the accessory or ancillary proteins to effectively carry out their function. Accessory proteins associate with cytoskeletal filaments and their monomers, aiding filament formation and function. They also help in the cross-communication among cytoskeletal filaments. Cytoskeletal accessory proteins are...


