Oncode Institute, Department of Cell and Chemical Biology, Leiden University Medical Center LUMC, Einthovenweg 20, 2300RC Leiden, The Netherlands.
J Cell Sci. 2023 Feb 15;136(4). doi: 10.1242/jcs.260101. Epub 2023 Feb 24.
The endolysosomal system comprises a dynamic constellation of vesicles working together to sense and interpret environmental cues and facilitate homeostasis. Integrating extracellular information with the internal affairs of the cell requires endosomes and lysosomes to be proficient in decision-making: fusion or fission; recycling or degradation; fast transport or contacts with other organelles. To effectively discriminate between these options, the endolysosomal system employs complex regulatory strategies that crucially rely on reversible post-translational modifications (PTMs) with ubiquitin (Ub) and ubiquitin-like (Ubl) proteins. The cycle of conjugation, recognition and removal of different Ub- and Ubl-modified states informs cellular protein stability and behavior at spatial and temporal resolution and is thus well suited to finetune macromolecular complex assembly and function on endolysosomal membranes. Here, we discuss how ubiquitylation (also known as ubiquitination) and its biochemical relatives orchestrate endocytic traffic and designate cargo fate, influence membrane identity transitions and support formation of membrane contact sites (MCSs). Finally, we explore the opportunistic hijacking of Ub and Ubl modification cascades by intracellular bacteria that remodel host trafficking pathways to invade and prosper inside cells.
内体溶酶体系统由一组动态的囊泡组成，共同作用以感知和解释环境线索，并促进体内平衡。将细胞外信息与细胞内部事务整合需要内体和溶酶体能够熟练地做出决策：融合或分裂；回收或降解；快速运输或与其他细胞器接触。为了有效地在这些选项之间做出区分，内体溶酶体系统采用了复杂的调控策略，这些策略主要依赖于泛素（Ub）和泛素样（Ubl）蛋白的可逆翻译后修饰（PTMs）。不同 Ub 和 Ubl 修饰状态的缀合、识别和去除循环为细胞内蛋白质的稳定性和行为提供了时空分辨率的信息，因此非常适合微调内体溶酶体膜上的大分子复合物组装和功能。在这里，我们讨论了泛素化（也称为 ubiquitination）及其生化相关物如何协调胞吞作用和指定货物命运、影响膜特性转换以及支持膜接触位点（MCS）的形成。最后，我们探讨了细胞内细菌对内体溶酶体系统的泛素和 Ubl 修饰级联的机会性劫持，这些细菌重塑了宿主运输途径，以入侵和在细胞内繁衍生息。
