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调控轴突生长和导向期间细胞器动态的分子机制。

Molecular machinery regulating organelle dynamics during axon growth and guidance.

机构信息

Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.

RIKEN Center for Brain Science, Wako, Saitama 351-0198, Japan.

出版信息

Semin Cell Dev Biol. 2023 Jan 15;133:3-9. doi: 10.1016/j.semcdb.2022.02.019. Epub 2022 Feb 25.

Abstract

Axon growth and guidance in the developing nervous system rely on intracellular membrane dynamics that involve endosome maturation and transport, as well as its regulated tethering to the endoplasmic reticulum (ER). Recent studies have identified several key molecules, such as protrudin, which plays a dynamic role at membrane contact sites between the ER and endosomes/lysosomes, and myosin Va, which acts as a sensor for ER-derived Ca that triggers peri-ER membrane export. These molecules form different types of multiprotein complexes at the interface of organelles and, in response to their surrounding microenvironments, such as Ca concentrations and lipid contents, regulate the directional movement of endosomal vesicles in extending axons. Here, we review the molecular mechanisms underlying membrane dynamics and inter-organelle interactions during neuronal morphogenesis.

摘要

在发育中的神经系统中,轴突的生长和导向依赖于细胞内的膜动态变化,这涉及到内体的成熟和运输,以及其与内质网(ER)的有调节的连接。最近的研究已经确定了几个关键分子,如突起蛋白(protrudin),它在 ER 和内体/溶酶体之间的膜接触位点处发挥动态作用,肌球蛋白 Va(myosin Va)作为 ER 衍生的 Ca 的传感器,触发 ER 周围膜的输出。这些分子在细胞器的界面处形成不同类型的多蛋白复合物,并根据其周围的微环境,如 Ca 浓度和脂质含量,调节延伸轴突中内体囊泡的定向运动。在这里,我们综述了神经元形态发生过程中膜动态和细胞器间相互作用的分子机制。

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