Article

A highly dynamic ER-derived phosphatidylinositol-synthesizing organelle supplies phosphoinositides to cellular membranes.

Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, National Institutes of Health, Bethesda, MD 20892, USA.
Developmental Cell (Impact Factor: 10.37). 11/2011; 21(5):813-24. DOI: 10.1016/j.devcel.2011.09.005
Source: PubMed

ABSTRACT Polyphosphoinositides are lipid signaling molecules generated from phosphatidylinositol (PtdIns) with critical roles in vesicular trafficking and signaling. It is poorly understood where PtdIns is located within cells and how it moves around between membranes. Here we identify a hitherto-unrecognized highly mobile membrane compartment as the site of PtdIns synthesis and a likely source of PtdIns of all membranes. We show that the PtdIns-synthesizing enzyme PIS associates with a rapidly moving compartment of ER origin that makes ample contacts with other membranes. In contrast, CDP-diacylglycerol synthases that provide PIS with its substrate reside in the tubular ER. Expression of a PtdIns-specific bacterial PLC generates diacylglycerol also in rapidly moving cytoplasmic objects. We propose a model in which PtdIns is synthesized in a highly mobile lipid distribution platform and is delivered to other membranes during multiple contacts by yet-to-be-defined lipid transfer mechanisms.

0 Bookmarks
 · 
83 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many ion channels and other membrane-associated proteins. To determine precursor sources of the PM PI(4,5)P2 pool in tsA-201 cells, we monitored KCNQ2/3 channel currents and translocation of PHPLCδ1 domains as real-time indicators of PM PI(4,5)P2, and translocation of PHOSH2×2, and PHOSH1 domains as indicators of PM and Golgi phosphatidylinositol 4-phosphate [PI(4)P], respectively. We selectively depleted PI(4)P pools at the PM, Golgi, or both using the rapamycin-recruitable lipid 4-phosphatases. Depleting PI(4)P at the PM with a recruitable 4-phosphatase (Sac1) results in a decrease of PI(4,5)P2 measured by electrical or optical indicators. Depleting PI(4)P at the Golgi with the 4-phosphatase or disrupting membrane-transporting motors induces a decline in PM PI(4,5)P2. Depleting PI(4)P simultaneously at both the Golgi and the PM induces a larger decrease of PI(4,5)P2. The decline of PI(4,5)P2 following 4-phosphatase recruitment takes 1-2 min. Recruiting the endoplasmic reticulum (ER) toward the Golgi membranes mimics the effects of depleting PI(4)P at the Golgi, apparently due to the trans actions of endogenous ER Sac1. Thus, maintenance of the PM pool of PI(4,5)P2 appears to depend on precursor pools of PI(4)P both in the PM and in the Golgi. The decrease in PM PI(4,5)P2 when Sac1 is recruited to the Golgi suggests that the Golgi contribution is ongoing and that PI(4,5)P2 production may be coupled to important cell biological processes such as membrane trafficking or lipid transfer activity.
    Proceedings of the National Academy of Sciences 05/2014; · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plants differ in many ways from mammals or yeast. However, plants employ phosphoinositides for the regulation of essential cellular functions as do all other eukaryotes. In recent years the plant phosphoinositide system has been linked to the control of cell polarity. Phosphoinositides are also implicated in plant adaptive responses to changing environmental conditions. The current understanding is that plant phosphoinositides control membrane trafficking, ion channels and the cytoskeleton in similar ways as in other eukaryotic systems, but adapted to meet plant cellular requirements and with some plant-specific features. In addition, the formation of soluble inositol polyphosphates from phosphoinositides is important for the perception of important phytohormones, as the relevant receptor proteins contain such molecules as structural cofactors. Overall, the essential nature of phosphoinositides in plants has been established. Still, the complexity of the phosphoinositide networks in plant cells is only emerging and invites further study of its molecular details. This article is part of a special issue entitled Phosphoinositides.
    Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 09/2014; · 4.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The lipid composition of cellular organelles is tailored to suit their specialized tasks. A fundamental transition in the lipid landscape divides the secretory pathway in early and late membrane territories, allowing an adaptation from biogenic to barrier functions. Defending the contrasting features of these territories against erosion by vesicular traffic poses a major logistical problem. To this end, cells evolved a network of lipid composition sensors and pipelines along which lipids are moved by non-vesicular mechanisms. We review recent insights into the molecular basis of this regulatory network and consider examples in which malfunction of its components leads to system failure and disease.
    Nature 06/2014; 510(7503):48-57. · 42.35 Impact Factor

Full-text (2 Sources)

Download
10 Downloads
Available from
Jul 9, 2014