Sánchez Noelia, Valle Rosario, Roncero César
Instituto de Biología Funcional y Genómica (IBFG) and Departamento de Microbiología y Genética, CSIC-Universidad de Salamanca, 37007 Salamanca, Spain.
J Fungi (Basel). 2025 Mar 14;11(3):221. doi: 10.3390/jof11030221.
Chitin synthase 3 complex assembly begins at the endoplasmic reticulum where the formation of a Chs3/Chs7 complex facilitates its exit from the ER and its transport along the secretory route. In the present study, our work shows that orphan molecules of Chs7 can exit the ER and are later recycled from the early Golgi by coat protein I (COPI) machinery via the adaptor complex Erv41/Erv46. Moreover, an eventual excess of the protein in the Golgi is recognized by the GGA complex and targeted to the vacuole for degradation through the ESCRT machinery. Non-oligomerizable versions of Chs3 can also exit the ER individually and follow a similar route to that of Chs7. We therefore demonstrate the traffic of unassembled CS3 subunits and describe the cellular mechanisms that guarantee the correct assembly of this protein complex at the ER while providing a default traffic route to the vacuole in case of its failure. This traffic route is shared with canonical ER adaptors, such as Erv29 and Erv14, and other components of protein complexes. The comparative analysis of their traffic allows us to discern a cellular program that combines COPI recycling, proteasomal degradation, and vacuolar disposal for maintaining protein homeostasis at the ER.
几丁质合酶3复合物的组装始于内质网，在那里Chs3/Chs7复合物的形成促进其从内质网中排出并沿分泌途径运输。在本研究中，我们的工作表明，Chs7的孤立分子可以从内质网中排出，随后通过衔接蛋白复合物Erv41/Erv46，由衣被蛋白I（COPI）机制从早期高尔基体中回收。此外，高尔基体中最终过量的蛋白质被GGA复合物识别，并通过ESCRT机制靶向液泡进行降解。不可寡聚化的Chs3版本也可以单独从内质网中排出，并遵循与Chs7相似的途径。因此，我们证明了未组装的CS3亚基的运输，并描述了在保证该蛋白复合物在内质网正确组装的同时，在其组装失败时提供一条通向液泡的默认运输途径的细胞机制。这条运输途径与典型的内质网衔接蛋白（如Erv29和Erv14）以及蛋白复合物的其他成分共享。对它们运输的比较分析使我们能够识别出一个细胞程序，该程序结合了COPI回收、蛋白酶体降解和液泡处理，以维持内质网的蛋白质稳态。
