Role of phosphatidylinositol 5-phosphate 4-kinase α in zebrafish development
Role of phosphatidylinositol 5-phosphate 4-kinase α in zebrafish development
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DOI：
10.1016/j.biocel.2013.03.009
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发表时间：
2013-07-01
影响因子：
4
通讯作者：
Haramis, Anna-Pavlina G.
中科院分区：
文献类型：
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作者：
Elouarrat, Dalila;van der Velden, Yme U.;Haramis, Anna-Pavlina G.
磷脂酰肌醇5-磷酸4激酶（PIP4Ks）磷酸化磷脂酰肌醇5-磷酸（PI5P）生成磷脂酰肌醇4,5-二磷酸；它们最有可能的功能是调节PI5P的水平，PI5P是一种被认为是信号传导的中间体。哺乳动物有三种PIP4Ks亚型（α， β和γ），但它们的生理作用仍然知之甚少。在本研究中，我们鉴定了高活性人类PIP4K α亚型的斑马鱼同源基因（zPIP4K α），并分析了其在胚胎发育中的作用。RT-PCR分析和全载原位杂交实验表明，zPIP4K α是母系表达的。在胚胎后期，在头部和胸鳍中检测到PIP4K α的高表达。反义morpholino寡核苷酸敲低zPIP4K α导致严重的形态学异常，包括48 hpf时的中体缠绕缺陷。至少在很大程度上，通过注射人PIP4K α mRNA可以挽救异常表型。我们的研究结果揭示了PIP4K α及其活性在脊椎动物组织稳态和器官发育中的关键作用。(C) 2013 Elsevier Ltd.版权所有。
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 (alpha, beta and gamma), but their physiological roles remain poorly understood. In the present study, we identified the zebrafish orthologue (zPIP4K alpha) of the high-activity human PIP4K alpha isoform and analyzed its role in embryonic development. RT-PCR analysis and whole-mount in situ hybridization experiments showed that zPIP4K alpha is maternally expressed. At later embryonic stages, high PIP4K alpha expression was detected in the head and the pectoral fins. Knockdown of zPIP4K alpha by antisense morpholino oligonucleotides led to severe morphological abnormalities, including midbody winding defects at 48 hpf. The abnormal phenotype could be rescued, at least in large part, by injection of human PIP4K alpha mRNA. Our results reveal a key role for PIP4K alpha and its activity in vertebrate tissue homeostasis and organ development. (C) 2013 Elsevier Ltd. All rights reserved.