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First published online December 9, 2004

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Sluggish PI3K output

Inositol lipids phosphorylated at the 3-OH position, such as PtdIns(3,4)P₂ and PtdIns(3,4,5)P₃, play important roles in cell migration, cell proliferation and membrane trafficking. Generated by PI 3-kinases in response to various stimuli, these 3-phosphoinositides recruit proteins containing PH, PX or FYVE domains to specific membrane sites, where they can regulate downstream signalling. Phosphatases including PTEN then switch off signalling by removing the 3-phosphate group. To characterize 3-phosphoinositide signalling in Dictyostelium chemotaxis and phagocytosis, Cornelius Weijer and co-workers have used GFP-tagged contracts containing various different PH domains to monitor these phospholipids (see p. 6497). Their approach yields several unexpected results. For example, it shows that phagocytosis and chemotactic signalling both involve generation of PtdIns(3,4,5)P₃ but only phagocytosis generates PtdIns(3,4)P₂ – PTEN presumably converts PtdIns(3,4,5)P₃ to PtdIns(4,5)P₂ before PtdIns(3,4)P₂ can be formed in chemotaxis. Perhaps the most interesting observation, however, is that PtdIns(3,4,5)P₃-binding PH domains from different proteins exhibit different localization patterns – probably because of their different binding affinities. This indicates that a single 3-phosphoinositide-generating signal can generate distinct spatiotemporal biological outputs.

Related articles in JCS:

In vivo analysis of 3-phosphoinositide dynamics during Dictyostelium phagocytosis and chemotaxis

Dirk Dormann, Gerti Weijer, Simon Dowler, and Cornelis J. Weijer
JCS 2004 117: 6497-6509. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content