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The nuclear membrane organization of leukotriene synthesis.

Leukotrienes (LTs) are signaling molecules derived from arachidonic acid that initiate and amplify innate and adaptive immunity. In turn, how their synthesis is organized on the nuclear envelope of myeloid cells in response to extracellular signals is not understood. We define the supramolecular architecture of LT synthesis by identifying the activation-dependent assembly of novel multiprotein complexes on the outer and inner nuclear membranes of mast cells. These complexes are centered on the integral membrane protein 5-Lipoxygenase-Activating Protein, which we identify as a scaffold protein for 5-Lipoxygenase, the initial enzyme of LT synthesis. We also identify these complexes in mouse neutrophils isolated from inflamed joints. Our studies reveal the macromolecular organization of LT synthesis.

Pubmed ID: 19075240

Authors

  • Mandal AK
  • Jones PB
  • Bair AM
  • Christmas P
  • Miller D
  • Yamin TT
  • Wisniewski D
  • Menke J
  • Evans JF
  • Hyman BT
  • Bacskai B
  • Chen M
  • Lee DM
  • Nikolic B
  • Soberman RJ

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

December 23, 2008

Associated Grants

  • Agency: NINDS NIH HHS, Id: 5P50 NS010828
  • Agency: NIA NIH HHS, Id: 5R01 AG08487
  • Agency: NIBIB NIH HHS, Id: 5R01 EB000768
  • Agency: NIGMS NIH HHS, Id: 5R01 GM61823
  • Agency: NIAID NIH HHS, Id: P01 AI065858
  • Agency: NIAID NIH HHS, Id: R01 AI 059746
  • Agency: NIAID NIH HHS, Id: R01 AI068771
  • Agency: NIAID NIH HHS, Id: R56 AI068771
  • Agency: NIDDK NIH HHS, Id: T32 DK001540

Mesh Terms

  • 5-Lipoxygenase-Activating Proteins
  • Animals
  • Arachidonate 5-Lipoxygenase
  • Arthritis
  • Carrier Proteins
  • Leukotrienes
  • Membrane Proteins
  • Mice
  • Multiprotein Complexes
  • Myeloid Cells
  • Neutrophils
  • Nuclear Envelope