Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Marseille F-13288, France.
Mol Biol Cell. 2010 Jun 1;21(11):1825-35. doi: 10.1091/mbc.e09-11-0976. Epub 2010 Apr 7.
Dictyostelium constitutes a genetically tractable model for the analysis of autophagic cell death (ACD). During ACD, Dictyostelium cells first transform into paddle cells and then become round, synthesize cellulose, vacuolize, and die. Through random insertional mutagenesis, we identified the receptor histidine kinase DhkM as being essential for ACD. Surprisingly, different DhkM mutants showed distinct nonvacuolizing ACD phenotypes. One class of mutants arrested ACD at the paddle cell stage, perhaps through a dominant-negative effect. Other mutants, however, progressed further in the ACD program. They underwent rounding and cellulose synthesis but stopped before vacuolization. Moreover, they underwent clonogenic but not morphological cell death. Exogenous 8-bromo-cAMP restored vacuolization and death. A role for a membrane receptor at a late stage of the ACD pathway is puzzling, raising questions as to which ligand it is a receptor for and which moieties it phosphorylates. Together, DhkM is the most downstream-known molecule required for this model ACD, and its distinct mutants genetically separate previously undissociated late cell death events.
集胞藻是分析细胞自噬性死亡（ACD）的一种遗传上可操作的模型。在 ACD 过程中，集胞藻细胞首先转化为桨形细胞，然后变成圆形，合成纤维素，空泡化，最后死亡。通过随机插入突变，我们鉴定出受体组氨酸激酶 DhkM 对 ACD 是必需的。令人惊讶的是，不同的 DhkM 突变体表现出明显的非空泡化 ACD 表型。一类突变体使 ACD 在桨形细胞阶段停滞，可能通过显性负效应。然而，其他突变体在 ACD 程序中进一步进展。它们经历了圆形和纤维素合成，但在空泡化之前停止。此外，它们经历了克隆形成但没有形态学细胞死亡。外源性 8-溴-cAMP 恢复了空泡化和死亡。膜受体在 ACD 途径的晚期阶段发挥作用令人费解，这引发了关于它是哪种配体的受体以及它磷酸化哪些部分的问题。DhkM 是这个模型 ACD 中所需的最下游已知分子，其不同的突变体在遗传上分离了以前未分离的晚期细胞死亡事件。
