Dendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen storage sites synchronising DC maturation and antigen presentation. Maturation of DCs is accompanied by the induction of the ubiquitin-like modifier FAT10 (also known as UBD), which localises to aggresomes, structures that are similar to DALIS. FAT10 is conjugated to substrate proteins and serves as a signal for their rapid and irreversible degradation by the 26S proteasome similar to, yet independently of ubiquitin, thereby contributing to antigen presentation. Here, we have investigated whether FAT10 is involved in the formation and turnover of DALIS, and whether proteins accumulating in DALIS can be modified through conjunction to FAT10 (FAT10ylated). We found that FAT10 localises to DALIS in maturing DCs and that this localisation occurs independently of its conjugation to substrates. Additionally, we investigated the DALIS turnover in FAT10-deficient and -proficient DCs, and observed FAT10-mediated disassembly of DALIS. Thus, we report further evidence that FAT10 is involved in antigen processing, which may provide a functional rationale as to why FAT10 is selectively induced upon DC maturation.

树突状细胞 (DC) 聚集体样诱导结构 (DALIS) 是多泛素化蛋白的蛋白质聚集体，在 DC 成熟过程中瞬时形成。DALIS 随机分散在整个细胞质中，并作为同步 DC 成熟和抗原呈递的抗原储存位点。DC 的成熟伴随着泛素样修饰剂 FAT10（也称为 UBD）的诱导，该修饰剂定位于聚集体，其结构与 DALIS 类似。FAT10 与底物蛋白缀合，作为底物蛋白被 26S 蛋白酶体快速且不可逆降解的信号，类似于但独立于泛素，从而有助于抗原呈递。在这里，我们研究了FAT10是否参与DALIS的形成和周转，以及DALIS中积累的蛋白质是否可以通过与FAT10结合而被修饰（FAT10化）。我们发现 FAT10 在成熟 DC 中定位于 DALIS，并且这种定位的发生独立于其与底物的缀合。此外，我们研究了 FAT10 缺陷和 FAT10 丰富的 DC 中的 DALIS 周转，并观察了 FAT10 介导的 DALIS 分解。因此，我们报告了 FAT10 参与抗原加工的进一步证据，这可能为为什么 FAT10 在 DC 成熟时被选择性诱导提供了功能原理。