Novel PI(4)P 5-kinase homologue, Fab1p, essential for normal vacuole function and morphology in yeast.
Novel PI(4)P 5-kinase homologue, Fab1p, essential for normal vacuole function and morphology in yeast.
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新型 PI(4)P 5-激酶同源物 Fab1p，对于酵母正常液泡功能和形态至关重要。
DOI：
10.1091/mbc.6.5.525
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发表时间：
1995
影响因子：
3.3
通讯作者：
Koshland,D
中科院分区：
文献类型：
--
作者：
Yamamoto,A;DeWald,DB;Boronenkov,IV;Anderson,RA;Emr,SD;Koshland,D
芽殖酵母的 FAB1 基因预计编码 257 kDa 的蛋白质，该蛋白质与人类 II 型 PI(4)P 5-激酶 (PIP5K-II) 表现出显着的序列同源性。最近克隆的人类 PIP5K-II 特异性地将 PI(4)P 转化为 PI(4,5)P2（Boronenkov 和 Anderson，1995）。 Fab1p 和 PIP5K-II 之间相似度最高的区域包括预测的核苷酸结合基序，该基序可能对应于蛋白质的催化结构域。有趣的是，PIP5K-II 和 Fab1p 均未与克隆的 PI 3-激酶或 PI 4-激酶表现出显着的同源性。 fab1 突变导致非倍体和双核细胞的形成（因此称为 FAB）。此外，Fab1p 功能的丧失会导致液泡功能和形态、细胞表面完整性和细胞生长的缺陷。对温度条件 fab1 突变体的实验表明，当细胞转移到不允许的温度时，它们的液泡迅速（30 分钟内）扩大到两倍以上。使用 fab1 ts 突变体进行的其他实验以及使用 fab1 vps（液泡蛋白分选缺陷）双突变体获得的结果表明，在 fab1 突变体中观察到的核分裂和细胞表面完整性缺陷是继发于液泡形态缺陷的。基于这些数据，我们提出 Fab1p 是一种 PI(4)P 5-激酶，并且 Fab1p 反应的产物 PIP2 可能通过控制进出液泡的膜通量来发挥液泡稳态的重要调节作用。此外，对影响 PI 代谢的 fab1 突变体和其他酵母突变体的表型进行比较表明，磷酸肌醇可以作为几种不同膜运输途径的通用调节剂。
The FAB1 gene of budding yeast is predicted to encode a protein of 257 kDa that exhibits significant sequence homology to a human type II PI(4)P 5-kinase (PIP5K-II). The recently cloned human PIP5K-II specifically converts PI(4)P to PI(4,5)P2 (Boronenkov and Anderson, 1995). The region of highest similarity between Fab1p and PIP5K-II includes a predicted nucleotide binding motif, which is likely to correspond to the catalytic domain of the protein. Interestingly, neither PIP5K-II nor Fab1p exhibit significant homology with cloned PI 3-kinases or PI 4-kinases. fab1 mutations result in the formation of aploid and binucleate cells (hence the name FAB). In addition, loss of Fab1p function causes defects in vacuole function and morphology, cell surface integrity, and cell growth. Experiments with a temperature conditional fab1 mutant revealed that their vacuoles rapidly (within 30 min) enlarge to more than double the size upon shifting cells to the nonpermissive temperature. Additional experiments with the fab1 ts mutant together with results obtained with fab1 vps (vacuolar protein sorting defective) double mutants indicate that the nuclear division and cell surface integrity defects observed in fab1 mutants are secondary to the vacuole morphology defects. Based on these data, we propose that Fab1p is a PI(4)P 5-kinase and that the product of the Fab1p reaction, PIP2, functions as an important regulator of vacuole homeostasis perhaps by controlling membrane flux to and/or from the vacuole. Furthermore, a comparison of the phenotypes of fab1 mutants and other yeast mutants affecting PI metabolism suggests that phosphoinositides may serve as general regulators of several different membrane trafficking pathways.