热重复蛋白HPO-27是一种溶酶体裂变因子
Letao Li1,2, Xilu Liu1,3, Shanshan Yang1,3
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Nature
|March 28, 2024
概括
研究人员发现HPO-27是溶酶体分裂的关键蛋白. 这一发现揭示了溶酶体如何分裂,影响细胞健康,发育和衰老.
科学领域:
- 细胞生物学
- 分子生物学
- 遗传学
背景情况:
- 溶酶体是细胞平衡,发育和衰老,调节降解和信号的重要器官.
- 溶酶体经历不断的融合和裂变,以适应它们的形态和功能.
- 控制溶酶体裂变的分子机制在很大程度上仍未被描述.
研究的目的:
- 识别和描述导致 lysosome 分裂的分子因素.
- 阐明HPO-27在Caenorhabditis elegans及其哺乳动物同类MROH1中调解溶酶分裂的机制.
主要方法:
- 使用了Caenorhabditis elegans作为一个模型生物.
- 使用超分辨率成像和负染色电子显微镜.
- 进行了体外溶解试验以研究蛋白质功能.
主要成果:
- 确定HPO-27,一个HEAT重复蛋白,作为一个关键的溶酶分裂因子.
- 通过RAB-7招募的HPO-27可以自组合并切断溶解体管.
- 展示了HPO-27及其人类同类MROH1在 lysosome裂变中的保存功能.
- 观察到HPO-27的损失导致溶酶体形态,完整性和降解受损,影响发育和寿命.
结论:
- HPO-27和MROH1是溶酶体分裂所必需的自组分离因子.
- 这些蛋白质在维持 lysosomal 稳态和功能方面发挥着至关重要的作用.
- HPO-27/MROH1的失调会影响细胞过程,发育和生物的寿命.
相关概念视频
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K
Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
Homologous Recombination
50.5K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.5K
Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K


