Figure 1.

Phosphoinositide subcellular distribution, metabolism, and protein effectors. (A) Subcellular distribution of PI species. PIs concentrate in cytosolic membranes, serving as discrete determinants of membrane identity. The predominant localization of particular PI species in subcellular compartments is depicted. There is some overlap of PI signature between membrane compartments, and heterogeneity of PI distribution on membrane compartments also occurs. PtdIns(4,5)P₂ and PtdIns(3,4,5)P₃ are enriched at the plasma membrane, possibly in raft-like domains. PtdIns(3,4)P₂ dominates in early endocytic membranes and at the plasma membrane. PtdIns(3)P is concentrated on early endosomal (EE) membranes, and the multivesicular body (MVB) compartment. PtdIns(4)P is enriched at the Golgi complex and in Golgi-derived carriers. PtdIns(3,5)P₂ concentrates on late compartments of the endocytic pathway, the MVB, and lysosome. PtdIns(5)P is localized in the nucleus, and generation of nuclear PtdIns(4,5)P₂ is key to regulating some aspects of gene expression (reviewed in Barlow et al. 2009). Parallels can be drawn between the generation of front–rear axis in migrating cells and apical–basal polarity in polarized cell types (for recent review, see Nelson 2009). Not all cellular compartments are illustrated and arrows are not intended to represent the entire cohort of known endocytic trafficking routes. Illustration based in part on data from Kutateladze (2010), with additional elements added. (B) Representation of the metabolic interconversions that generate the seven phosphoinositide species from PtdIns. Kinases and phosphatases involved in generating the PIs involved in apical and basolateral membrane identity are indicated. (C) PI binding modules present in cytosolic effectors and their reported PI binding preferences. The family of PI “code-breaking” modules includes PH, ANTH (AP180 amino-terminal homology), C2 (conserved region 2 of protein kinase C), ENTH (epsin amino-terminal homology), FERM (band 4.1, Ezrin, Radixin, Moesin), FYVE (Fab1, YOTB, Vac1, and EEA1), GOLPH3 (Golgi phosphoprotein 3), PROPPINS (B-propellors that bind PIs), PTB (phosphotyrosine binding), PX (Phox homology), and Tubby modules. Examples of protein interactions with different PIs are provided. (Panel based in part on data from DiPaolo and Di Camilli 2006; McCrea and De Camilli 2009; and Kutateladze 2010.)