The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transport.
The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transport.
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DOI：
10.1242/jcs.03153
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发表时间：
2006-10-01
影响因子：
4
通讯作者：
Cullen PJ
中科院分区：
文献类型：
--
作者：
Rutherford AC;Traer C;Wassmer T;Pattni K;Bujny MV;Carlton JG;Stenmark H;Cullen PJ
酵母基因FAB1和其哺乳动物同源基因Pip5k3分别编码磷脂酰肌醇3-磷酸[PtdIns(3)P]5-激酶Fab1p和PIKfyve，这两种酶产生磷脂酰肌醇3，5-二磷酸[PtdIns(3，5)P2]。FAB1Δ酵母细胞和哺乳动物细胞过表达激酶死亡的PIKfyve突变体的一个共同特征是形成肿胀的空泡表型：这种表型表明这些酶及其产物PtdIns(3，5)P2在调节内膜动态平衡方面具有保守的功能。在目前的研究中，固定和活细胞成像已经确定，当在HeLa细胞中低水平过度表达时，PIKfyve主要与早期内膜室的动态管状和囊泡成分有关。此外，通过使用小干扰RNA，已经表明抑制PIKfyve可以诱导形成肿胀的内体结构，从而维持其早期和晚期的内体特性。尽管在PIKfyve抑制的细胞中，表皮生长因子和转铁蛋白受体的内化、循环和降解性分选没有受到干扰，但观察到内体到跨高尔基网络(TGN)的逆行运输存在明显的缺陷。这些数据表明，PIKfyve主要与早期的内体有关，从那里它调节逆行的膜运输到TGN。因此，在PIKfyve抑制的细胞中观察到的肿胀的内体表型主要是由于逆行膜分裂的减少，而不是多囊泡体生物发生的缺陷。
The yeast gene fab1 and its mammalian orthologue Pip5k3 encode the phosphatidylinositol 3-phosphate [PtdIns(3)P] 5-kinases Fab1p and PIKfyve, respectively, enzymes that generates phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2]. A shared feature of fab1Δ yeast cells and mammalian cells overexpressing a kinase-dead PIKfyve mutant is the formation of a swollen vacuolar phenotype: a phenotype that is suggestive of a conserved function for these enzymes and their product, PtdIns(3,5)P2, in the regulation of endomembrane homeostasis. In the current study, fixed and live cell imaging has established that, when overexpressed at low levels in HeLa cells, PIKfyve is predominantly associated with dynamic tubular and vesicular elements of the early endosomal compartment. Moreover, through the use of small interfering RNA, it has been shown that suppression of PIKfyve induces the formation of swollen endosomal structures that maintain their early and late endosomal identity. Although internalisation, recycling and degradative sorting of receptors for epidermal growth factor and transferrin was unperturbed in PIKfyve suppressed cells, a clear defect in endosome to trans-Golgi-network (TGN) retrograde traffic was observed. These data argue that PIKfyve is predominantly associated with the early endosome, from where it regulates retrograde membrane trafficking to the TGN. It follows that the swollen endosomal phenotype observed in PIKfyve-suppressed cells results primarily from a reduction in retrograde membrane fission rather than a defect in multivesicular body biogenesis.
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影响因子：
4.8
作者：
Cozier, GE;Carlton, J;Cullen, PJ
通讯作者：
Cullen, PJ
影响因子：
3.3
作者：
Ikonomov, OC;Sbrissa, D;Shisheva, A
通讯作者：
Shisheva, A
DOI：
10.1083/jcb.143.1.65
发表时间：
1998-10-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gary JD;Wurmser AE;Bonangelino CJ;Weisman LS;Emr SD
通讯作者：
Emr SD
影响因子：
19
作者：
Griffiths, G;Gruenberg, J
通讯作者：
Gruenberg, J
DOI：
10.1083/jcb.109.6.3303
发表时间：
1989-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dunn KW;McGraw TE;Maxfield FR
通讯作者：
Maxfield FR