Skip to Content
Merck
  • Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis.

Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis.

Molecular cell (2019-08-14)
Taki Nishimura, Michael Gecht, Roberto Covino, Gerhard Hummer, Michal A Surma, Christian Klose, Hiroyuki Arai, Nozomu Kono, Christopher J Stefan
ABSTRACT

The plasma membrane (PM) is composed of a complex lipid mixture that forms heterogeneous membrane environments. Yet, how small-scale lipid organization controls physiological events at the PM remains largely unknown. Here, we show that ORP-related Osh lipid exchange proteins are critical for the synthesis of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2], a key regulator of dynamic events at the PM. In real-time assays, we find that unsaturated phosphatidylserine (PS) and sterols, both Osh protein ligands, synergistically stimulate phosphatidylinositol 4-phosphate 5-kinase (PIP5K) activity. Biophysical FRET analyses suggest an unconventional co-distribution of unsaturated PS and phosphatidylinositol 4-phosphate (PI4P) species in sterol-containing membrane bilayers. Moreover, using in vivo imaging approaches and molecular dynamics simulations, we show that Osh protein-mediated unsaturated PI4P and PS membrane lipid organization is sensed by the PIP5K specificity loop. Thus, ORP family members create a nanoscale membrane lipid environment that drives PIP5K activity and PI(4,5)P2 synthesis that ultimately controls global PM organization and dynamics.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
4-(Dimethylamino)benzaldehyde, suitable for histochemical demonstration of nitro blue tetrazolium reduction in neutrophils
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sulfuric acid, 99.999%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ammonium molybdate, 99.98% trace metals basis
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
1-Butyl-3-methylimidazolium hexafluorophosphate, ≥97.0% (HPLC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Glass beads, acid-washed, 212-300 μm (50-70 U.S. sieve)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Imidazole, ReagentPlus®, 99%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Imidazole, ReagentPlus®, 99%, Redi-Dri, free-flowing
SKU
Pack Size
Availability
Price
Quantity
Avanti
17:0-20:4 PI(3,4,5)P3, Avanti Research - A Croda Brand LM1906, powder
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
ECO TWEEN® 80, viscous liquid
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
TWEEN® 80, viscous liquid
SKU
Pack Size
Availability
Price
Quantity
Supelco
Malachite Green chloride, analytical standard
SKU
Pack Size
Availability
Price
Quantity
Avanti
17:0-20:4 PI(4,5)P2, Avanti Research - A Croda Brand LM1904, powder
SKU
Pack Size
Availability
Price
Quantity
Avanti
16:0-18:1 PI(4)P, Avanti Research - A Croda Brand 850157P, powder
SKU
Pack Size
Availability
Price
Quantity