Calvo-Garrido Javier, Carilla-Latorre Sergio, Lázaro-Diéguez Francisco, Egea Gustavo, Escalante Ricardo
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Mol Biol Cell. 2008 Aug;19(8):3442-53. doi: 10.1091/mbc.e08-01-0075. Epub 2008 Jun 11.
Vacuole membrane protein 1 (Vmp1) is membrane protein of unknown molecular function that has been associated with pancreatitis and cancer. The social amoeba Dictyostelium discoideum has a vmp1-related gene that we identified previously in a functional genomic study. Loss-of-function of this gene leads to a severe phenotype that compromises Dictyostelium growth and development. The expression of mammalian Vmp1 in a vmp1(-) Dictyostelium mutant complemented the phenotype, suggesting a functional conservation of the protein among evolutionarily distant species and highlights Dictyostelium as a valid experimental system to address the function of this gene. Dictyostelium Vmp1 is an endoplasmic reticulum protein necessary for the integrity of this organelle. Cells deficient in Vmp1 display pleiotropic defects in the secretory pathway and organelle biogenesis. The contractile vacuole, which is necessary to survive under hypoosmotic conditions, is not functional in the mutant. The structure of the Golgi apparatus, the function of the endocytic pathway and conventional protein secretion are also affected in these cells. Transmission electron microscopy of vmp1(-) cells showed the accumulation of autophagic features that suggests a role of Vmp1 in macroautophagy. In addition to these defects observed at the vegetative stage, the onset of multicellular development and early developmental gene expression are also compromised.
液泡膜蛋白1（Vmp1）是一种分子功能未知的膜蛋白，与胰腺炎和癌症相关。社会变形虫盘基网柄菌有一个我们先前在功能基因组研究中鉴定出的与vmp1相关的基因。该基因的功能丧失会导致严重的表型，损害盘基网柄菌的生长和发育。哺乳动物Vmp1在vmp1（-）盘基网柄菌突变体中的表达弥补了该表型，这表明该蛋白在进化距离较远的物种间具有功能保守性，并突出了盘基网柄菌作为研究该基因功能的有效实验系统。盘基网柄菌Vmp1是内质网完整性所必需的内质网蛋白。缺乏Vmp1的细胞在分泌途径和细胞器生物发生方面表现出多效性缺陷。在低渗条件下生存所必需的收缩泡在突变体中无功能。这些细胞中高尔基体的结构、内吞途径的功能和常规蛋白质分泌也受到影响。vmp1（-）细胞的透射电子显微镜观察显示自噬特征的积累，这表明Vmp1在巨自噬中起作用。除了在营养阶段观察到的这些缺陷外，多细胞发育的起始和早期发育基因表达也受到损害。
