Phosphatidylinositol 3,5-bisphosphate: metabolism and cellular functions

Robert Michell, Victoria Heath, MA Lemmon, Stephen Dove

Research output: Contribution to journalReview article

181 Citations (Scopus)


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(2)] are in membrane and protein trafficking, and in pH control in the endosome-lysosome axis. Recently identified PtdIns(3,5)P(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(2). The importance of PtdIns(3,5)P(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(2) dysfunction in the human genetic conditions X-linked myotubular myopathy, Type-4B Charcot-Marie-Tooth disease and fleck corneal dystrophy.
Original languageEnglish
Pages (from-to)52-63
Number of pages12
JournalTrends in Biochemical Sciences
Issue number1
Publication statusPublished - 1 Jan 2006


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