Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Int J Biochem Cell Biol. 2013 Jul;45(7):1293-301. doi: 10.1016/j.biocel.2013.03.009. Epub 2013 Mar 26.
Phosphatidylinositol 5-phosphate 4-kinases (PIP4Ks) phosphorylate phosphatidylinositol 5-phosphate (PI5P) to generate phosphatidylinositol 4,5-bisphosphate; their most likely function is the regulation of the levels of PI5P, a putative signalling intermediate. There are three mammalian PIP4Ks isoforms (α, β and γ), but their physiological roles remain poorly understood. In the present study, we identified the zebrafish orthologue (zPIP4Kα) of the high-activity human PIP4K α isoform and analyzed its role in embryonic development. RT-PCR analysis and whole-mount in situ hybridization experiments showed that zPIP4Kα is maternally expressed. At later embryonic stages, high PIP4Kα expression was detected in the head and the pectoral fins. Knockdown of zPIP4Kα by antisense morpholino oligonucleotides led to severe morphological abnormalities, including midbody winding defects at 48hpf. The abnormal phenotype could be rescued, at least in large part, by injection of human PIP4Kα mRNA. Our results reveal a key role for PIP4Kα and its activity in vertebrate tissue homeostasis and organ development.
磷脂酰肌醇 5-磷酸 4-激酶（PIP4Ks）将磷脂酰肌醇 5-磷酸（PI5P）磷酸化生成磷脂酰肌醇 4,5-二磷酸；它们最可能的功能是调节 PI5P 的水平，PI5P 是一种假定的信号中间物。哺乳动物中有三种 PIP4K 同工型（α、β和γ），但其生理功能仍知之甚少。在本研究中，我们鉴定了斑马鱼同源物（zPIP4Kα）的高活性人 PIP4Kα 同工型，并分析了其在胚胎发育中的作用。RT-PCR 分析和整体原位杂交实验表明 zPIP4Kα 呈母源表达。在胚胎发育的后期，在头部和胸鳍中检测到高表达的 PIP4Kα。通过反义吗啉代寡核苷酸进行 zPIP4Kα 敲低导致严重的形态异常，包括 48hpf 时的中体卷曲缺陷。异常表型至少在很大程度上可以通过注射人 PIP4Kα mRNA 得到挽救。我们的研究结果揭示了 PIP4Kα 及其在脊椎动物组织稳态和器官发育中的活性的关键作用。
