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 arc...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 105; no. 51; pp. 20434 - 20439
Main Authors Mandal, Asim K, Jones, Phillip B, Bair, Angela M, Christmas, Peter, Miller, Douglas, Yamin, Ting-ting D, Wisniewski, Douglas, Menke, John, Evans, Jilly F, Hyman, Bradley T, Bacskai, Brian, Chen, Mei, Lee, David M, Nikolic, Boris, Soberman, Roy J
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 23.12.2008
National Acad Sciences
Subjects
5-Lipoxygenase-Activating Proteins
Animals
Arachidonate 5-Lipoxygenase - metabolism
Arthritis - enzymology
Arthritis - metabolism
Biochemistry
Biological Sciences
Carrier Proteins - metabolism
Cell membranes
Cell nucleus
Cells
Enzymes
Leukotrienes
Leukotrienes - biosynthesis
Mast cells
Membrane Proteins - analysis
Membrane Proteins - metabolism
Membranes
Mice
Molecules
Multiprotein Complexes - analysis
Myeloid Cells - chemistry
Myeloid Cells - metabolism
Neutrophils
Neutrophils - chemistry
Neutrophils - metabolism
Nuclear Envelope - chemistry
Nuclear Envelope - metabolism
Nuclear interactions
Nuclear membrane
Pixels
Protein synthesis
Proteins
Signal transduction
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Summary: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.
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Edited by K. Frank Austen, Brigham and Women's Hospital, Boston, MA, and approved November 4, 2008
Author contributions: A.K.M., P.B.J., P.C., J.F.E., B.T.H., B.B., M.C., D.M.L., and R.J.S. designed research; A.K.M., P.B.J., M.C., and D.M.L. performed research; D.M., T.-t.D.Y., D.W., and J.M. contributed new reagents/analytic tools; A.K.M., P.B.J., A.M.B., P.C., D.M., T.-t.D.Y., D.W., J.M., J.F.E., B.T.H., B.B., M.C., D.M.L., B.N., and R.J.S. analyzed data; and A.K.M., P.B.J., A.M.B., J.F.E., and R.J.S. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0808211106