Phosphatidylinositol 3,5-bisphosphate: metabolism and cellular functions

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tibs.2005.11.013 Byline: Robert H. Michell (a), Victoria L. Heath (a), Mark A. Lemmon (b), Stephen K. Dove (a) Abstract: Polyphosphoinositides (PPIn) are low-abundance membrane phospholipids that each bind to a distinctive set of effector proteins and, thereby, regulate a characteristic suite of cellular processes. Major functions of phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P.sub.2] are in membrane and protein trafficking, and in pH control in the endosome-lysosome axis. Recently identified PtdIns(3,5)P.sub.2 effectors include a family of novel [beta]-propeller proteins, for which we propose the name PROPPINs [for [beta]-propeller(s) that binds PPIn], and possibly proteins of the epsin and CHMP (charged multi-vesicular body proteins) families. All eukaryotes, with the exception of some pathogenic protists and microsporidians, possess proteins needed for the formation, metabolism and functions of PtdIns(3,5)P.sub.2. The importance of PtdIns(3,5)P.sub.2 for normal cell function is underscored by recent evidence for its involvement in mammalian cell responses to insulin and for PtdIns(3,5)P.sub.2 dysfunction in the human genetic conditions X-linked myotubular myopathy, Type-4B Charcot-Marie-Tooth disease and fleck corneal dystrophy. Author Affiliation: (a) School of Biosciences, University of Birmingham, Birmingham, UK, B15 2TT (b) Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA