title: The nuclear membrane organization of leukotriene synthesis.
abstract: 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.
authors.affiliation: Renal Unit, Massachusetts General Hospital, Building 149-The Navy Yard, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Asim K
authors.initials: AK
authors.lastname: Mandal
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Jones
authors.forename: Angela M
authors.initials: AM
authors.lastname: Bair
authors.forename: Peter
authors.initials: P
authors.lastname: Christmas
authors.forename: Douglas
authors.initials: D
authors.lastname: Miller
authors.forename: Ting-ting D
authors.initials: TT
authors.lastname: Yamin
authors.forename: Douglas
authors.initials: D
authors.lastname: Wisniewski
authors.forename: John
authors.initials: J
authors.lastname: Menke
authors.forename: Jilly F
authors.initials: JF
authors.lastname: Evans
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Brian
authors.initials: B
authors.lastname: Bacskai
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
authors.forename: Boris
authors.initials: B
authors.lastname: Nikolic
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Soberman
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001168:Arthritis / Q000201:enzymology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D015289:Leukotrienes / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000032:analysis*; D022423:Myeloid Cells / Q000737:chemistry / Q000378:metabolism; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism; D009685:Nuclear Envelope / Q000737:chemistry / Q000378:metabolism*
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548593:Alox5ap protein, mouse; D002352:Carrier Proteins; D015289:Leukotrienes; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D001094:Arachidonate 5-Lipoxygenase