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

Renal Unit, Massachusetts General Hospital, Building 149-The Navy Yard, 13th Street, Charlestown, MA 02129, USA.

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.

Mesh Terms:
5-Lipoxygenase-Activating Proteins, Animals, Arachidonate 5-Lipoxygenase, Arthritis, Carrier Proteins, Leukotrienes, Membrane Proteins, Mice, Multiprotein Complexes, Myeloid Cells, Neutrophils, Nuclear Envelope

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