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Phosphatidylinositol‐4‐phosphate synthesis and turnover spans multiple membrane compartments (999.2)
Author(s) -
Hammond Gerry,
Machner Matthias,
Balla Tamas
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.999.2
Subject(s) - golgi apparatus , phosphatase , endosome , microbiology and biotechnology , organelle , golgi membrane , phosphatidylinositol , effector , biology , kinase , secretory pathway , compartment (ship) , transmembrane protein , function (biology) , chemistry , biochemistry , phosphorylation , endoplasmic reticulum , receptor , intracellular , oceanography , geology
Organelle identity may be assisted by a phosphoinositide (PI) code, wherein specific PI lipids act as molecular “signposts”, ensuring exclusive recruitment of binding proteins to the correct membrane compartment. One example is PtdIns4 P , whose known effector proteins are recruited to the Golgi. However, the PI 4‐kinases (PI4K) that make PtdIns4 P belie such a restricted function, since they act at the Golgi, plasma membrane (PM) and in lysosomal traffic. To reconcile this contradiction, we re‐examined the distribution of PtdIns4 P with a novel biosensor derived from the P4M domain of L. pneumophila SidM. P4M localizes to the Golgi, PM and dynamic Rab7‐positive late endosomes/lysosomes. Chemically‐induced recruitment of PI phosphatases to these compartments demonstrates PtdIns4 P is the lipid bound in each case. Whereas the bulk of another PI lipid, PtdIns(4,5) P 2 is localized at the PM, it could be produced in the other PtdIns4 P ‐containing compartments by recruitment of a PtdIns4 P 5‐kinase. P4M can also detect ectopically produced PtdIns4 P on ER‐derived membranes. We show that each of the four PI4Ks overlap with pools of PtdIns4 P , and the ER/Golgi localized PtdIns4 P phosphatase, Sacm1l, hydrolyses both Golgi and PM pools. We conclude that PtdIns4 P has a much more complex function than as a simple molecular signpost for the Golgi, and likely functions through several as yet unappreciated protein interactions. Grant Funding Source : Intramural Research Program of the Eunice Kennedy Shriver NICHD, NIH