The structure of divalent cation-induced aggregates of PIP2 and their alteration by gelsolin and tau.
Phosphatidylinositol bisphosphate (PIP2) serves as a precursor for diacylglycerol and inositol trisphosphate in signal transduction cascades and regulates the activities of several actin binding proteins that influence the organization of the actin cytoskeleton. Molecules of PIP2 form 6-nm diameter micelles in water, but aggregate into larger, multilamellar structures in physiological concentrations of divalent cations. Electron microscopic analysis of these aggregates reveals that they are clusters of striated filaments, suggesting that PIP2 aggregates form stacks of discoid micelles rather than multilamellar vesicles or inverted hexagonal arrays as previously inferred from indirect observations. The distance between striations within the filaments varies from 4.2 to 5.4 nm and the diameter of the filaments depends on the dehydrated ionic radius of the divalent cation, with average diameters of 19, 12, and 10 nm for filaments formed by Mg2+, Ca2+, and Ba2+, respectively. The structure of the divalent cation-induced aggregates can be altered by PIP2 binding proteins. Gelsolin and the microtubule associated protein tau both affect the formation of aggregates, indicating that tau acts as a PIP2 binding protein in a manner similar to gelsolin. In contrast, another PIP2 binding protein, profilin, does not modify the aggregates.
Flanagan
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LA
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. flanagan@calvin.bwh.harvard.edu
Cunningham
C C
CC
Chen
J
J
Prestwich
G D
GD
Kosik
K S
KS
Janmey
P A
PA
D001464:Barium; D002118:Calcium; D002413:Cations, Divalent; D018260:Gelsolin / Q000737:chemistry* / Q000648:ultrastructure; D008274:Magnesium; D008823:Micelles; D008854:Microscopy, Electron; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry*; D011485:Protein Binding; D012542:Scattering, Radiation; D016875:tau Proteins / Q000737:chemistry* / Q000648:ultrastructure
D002413:Cations, Divalent; D018260:Gelsolin; D008823:Micelles; D019269:Phosphatidylinositol 4,5-Diphosphate; D016875:tau Proteins; D001464:Barium; D008274:Magnesium; D002118:Calcium