These authors contributed equally to this work.
Phosphatidylinositol-3,5-Bisphosphate: No Longer the Poor PIP2
Article first published online: 27 JUL 2011
© 2011 John Wiley & Sons A/S
Volume 13, Issue 1, pages 1–8, January 2012
How to Cite
Ho, C. Y., Alghamdi, T. A. and Botelho, R. J. (2012), Phosphatidylinositol-3,5-Bisphosphate: No Longer the Poor PIP2. Traffic, 13: 1–8. doi: 10.1111/j.1600-0854.2011.01246.x
- Issue published online: 8 DEC 2011
- Article first published online: 27 JUL 2011
- Accepted manuscript online: 7 JUL 2011 08:46AM EST
- Received 10 March 2011, revised and accepted for publication 6 July 2011, uncorrected manuscript published online 7 July 2011, published online 27 July 2011
- intracellular signaling;
- lipid kinase;
- membrane trafficking;
- organelle identity;
Phosphoinositides play an important role in organelle identity by recruiting effector proteins to the host membrane organelle, thus decorating that organelle with molecular identity. Phosphatidylinositol-3,5-bisphos- phate [PtdIns(3,5)P2] is a low-abundance phosphoinositide that predominates in endolysosomes in higher eukaryotes and in the yeast vacuole. Compared to other phosphoinositides such as PtdIns(4,5)P2, our understanding of the regulation and function of PtdIns(3,5)P2 remained rudimentary until more recently. Here, we review many of the recent developments in PtdIns(3,5)P2 function and regulation. PtdIns(3,5)P2 is now known to espouse functions, not only in the regulation of endolysosome morphology, trafficking and acidification, but also in autophagy, signaling mediation in response to stresses and hormonal cues and control of membrane and ion transport. In fact, PtdIns(3,5)P2 misregulation is now linked with several human neuropathologies including Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis. Given the functional versatility of PtdIns(3,5)P2, it is not surprising that regulation of PtdIns(3,5)P2 metabolism is proving rather elaborate. PtdIns(3,5)P2 synthesis and turnover are tightly coupled via a protein complex that includes the Fab1/PIKfyve lipid kinase and its antagonistic Fig4/Sac3 lipid phosphatase. Most interestingly, many PtdIns(3,5)P2 regulators play simultaneous roles in its synthesis and turnover.