PDZD8促进ER-lysosome膜接触点的自,以调节活动依赖的突触生长
Rajan S Thakur1, Kate M O'Connor-Giles2
1Department of Neuroscience, Brown University, Providence, RI, USA.
Cell reports
|March 29, 2025
概括
PDZD8蛋白对于神经系统中的突触连接至关重要,调节活动依赖的结节形成,并在突触生长期间促进细胞需求的自.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 突触连接需要复杂的细胞协调,膜接触点 (MCS) 作为信号中心.
- 对于MCSs在神经系统发育中的作用,特别是涉及到内分泌网膜 (ER),尚不清楚.
- PDZD8是一种与智力障碍相关的ER MCS绑定蛋白,在神经系统中具有未明确的功能.
研究的目的:
- 为了研究PDZD8在发育中的神经系统中的体内功能.
- 确定PDZD8在突触发育中的作用及其与自的关系.
主要方法:
- 通过多种实验范式在体内研究PDZD8的功能.
- 研究了PDZD8对活动依赖性突触形成的影响.
- 评估了PDZD8对ER-late内体/内体MCS的自流和溶酶体成熟的影响.
主要成果:
- PDZD8对于活动依赖的突触形成至关重要.
- 通过自,PDZD8可以诱导过度的突触结块形成.
- 当自受限时,PDZD8对于突触发育是必需的.
- PDZD8通过促进ER-late内体/内体MCS中的溶酶体成熟来增强自流.
结论:
- 通过调节突触连接,PDZD8在神经系统发育中起着至关重要的作用.
- 在高细胞需求期间,PDZD8的功能是促进自,例如在活动依赖的突触生长期间.
- PDZD8将ER-lysosome膜接触部位与神经元发育的自调节联系起来.
相关概念视频
01:45ER Retrieval Pathway
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
01:36Delivery 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...
01:27Autophagy
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,...
01:22Lysosomal Hydrolases
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,...
01:37The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
01:18Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...