Abstract:
:Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small-molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5-bisphosphate. Acute treatment of cells with YM201636 shows that the PIKfyve pathway is involved in the sorting of endosomal transport, with inhibition leading to the accumulation of a late endosomal compartment and blockade of retroviral exit. Inhibitor specificity is shown by the use of short interfering RNA against the target, as well as by rescue with the drug-resistant yeast orthologue Fab1. We concluded that the phosphatidylinositol 3,5-bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Jefferies HB,Cooke FT,Jat P,Boucheron C,Koizumi T,Hayakawa M,Kaizawa H,Ohishi T,Workman P,Waterfield MD,Parker PJdoi
10.1038/sj.embor.7401155subject
Has Abstractpub_date
2008-02-01 00:00:00pages
164-70issue
2eissn
1469-221Xissn
1469-3178pii
7401155journal_volume
9pub_type
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