自细胞前体的成熟需要同型的融合
Kevin Moreau1, Brinda Ravikumar, Maurizio Renna
1Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 20Y, UK.
Cell
|July 26, 2011
概括
自包括溶酶体在自细胞体内降解细胞废物. 这项研究表明,由SNARE蛋白质介导的早期Atg16L1前体融合对自细胞形成和成熟至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 自是一种通过 lysosomes 降解细胞质成分的基本细胞过程.
- 自细胞,双膜囊泡是自细胞的中心,起源于细胞.
- 准确的机制,规范的孔延长和自细胞成熟仍然不完全理解.
研究的目的:
- 阐明早期自细胞生物发生的基础分子机制.
- 研究Atg16L1前体成熟在自细胞形成中的作用.
- 确定参与早期自结构同型融合的关键蛋白质.
主要方法:
- 研究了Atg16L1在自细胞形成中的作用.
- 利用SNARE蛋白相互作用研究膜融合事件.
- 分析了同型融合对囊泡大小和成熟的影响.
主要成果:
- 证明早期Atg16L1前体的同型融合对自细胞形成至关重要.
- 确定了SNARE蛋白VAMP7及其合作伙伴对于Atg16L1前体同型融合至关重要.
- 表明这种融合事件调节了囊泡大小,影响到成长为LC3阳性自细胞.
结论:
- Atg16L1前体的同型融合是自的关键早期步骤.
- 这种依赖于VAMP7和合作伙伴SNARE的融合过程,将膜收购与自细胞生物生成相结合.
- 在这个阶段调节囊泡大小是随后自细胞成熟的关键.
相关概念视频
Maturation of Endosomes
The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
Changes in location
The maturing endosome moves along microtubules from the periphery of the cell towards the perinuclear region. This movement of the...
Changes in location
The maturing endosome moves along microtubules from the periphery of the cell towards the perinuclear region. This movement of the...
Autophagy
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Intralumenal Vesicles and Multivesicular Bodies
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
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...
Delivery Pathways to the Lysosome
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Mitochondrial Precursor Proteins
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
Most of the mitochondrial precursors...


