A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding.

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 Rep

journal_title

EMBO reports

authors

Jefferies HB,Cooke FT,Jat P,Boucheron C,Koizumi T,Hayakawa M,Kaizawa H,Ohishi T,Workman P,Waterfield MD,Parker PJ

doi

10.1038/sj.embor.7401155

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

164-70

issue

2

eissn

1469-221X

issn

1469-3178

pii

7401155

journal_volume

9

pub_type

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