The nuclear membrane organization of leukotriene synthesis

AK Mandal, PB Jones, AM Bair… - Proceedings of the …, 2008 - National Acad Sciences
AK Mandal, PB Jones, AM Bair, P Christmas, D Miller, TD Yamin, D Wisniewski, J Menke…
Proceedings of the National Academy of Sciences, 2008National Acad Sciences
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 …
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.
National Acad Sciences