Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA.
Genetics. 2012 Jun;191(2):461-75. doi: 10.1534/genetics.112.139667. Epub 2012 Mar 16.
The vacuolar-type ATPase (V-ATPase) is a proton pump composed of two sectors, the cytoplasmic V(1) sector that catalyzes ATP hydrolysis and the transmembrane V(o) sector responsible for proton translocation. The transmembrane V(o) complex directs the complex to different membranes, but also has been proposed to have roles independent of the V(1) sector. However, the roles of the V(1) sector have not been well characterized. In the nematode Caenorhabditis elegans there are two V(1) B-subunit genes; one of them, vha-12, is on the X chromosome, whereas spe-5 is on an autosome. vha-12 is broadly expressed in adults, and homozygotes for a weak allele in vha-12 are viable but are uncoordinated due to decreased neurotransmission. Analysis of a null mutation demonstrates that vha-12 is not required for oogenesis or spermatogenesis in the adult germ line, but it is required maternally for early embryonic development. Zygotic expression begins during embryonic morphogenesis, and homozygous null mutants arrest at the twofold stage. These mutant embryos exhibit a defect in the clearance of apoptotic cell corpses in vha-12 null mutants. These observations indicate that the V(1) sector, in addition to the V(o) sector, is required in exocytic and endocytic pathways.
液泡型 ATP 酶(V-ATPase)是一种质子泵,由两个部分组成,细胞质 V(1)部分催化 ATP 水解,跨膜 V(o)部分负责质子转运。跨膜 V(o)复合物将复合物引导到不同的膜上,但也被提议具有与 V(1)部分独立的作用。然而,V(1)部分的作用尚未得到很好的描述。在线虫秀丽隐杆线虫中有两个 V(1) B 亚基基因;其中一个,vha-12,位于 X 染色体上,而 spe-5 位于常染色体上。vha-12 在成体中广泛表达,vha-12 弱等位基因的纯合子是可行的,但由于神经传递减少而不协调。对缺失突变的分析表明,vha-12 不需要在成体生殖系中的卵子发生或精子发生中,但它需要母体来进行早期胚胎发育。合子表达在胚胎形态发生期间开始,纯合子缺失突变体在两倍期停止。这些突变体胚胎在 vha-12 缺失突变体中表现出清除凋亡细胞尸体的缺陷。这些观察表明,V(1)部分,除了 V(o)部分,在胞吐和胞吞途径中都是必需的。