Ceramide-rich microdomains facilitate nuclear envelope budding for non-conventional exosome formation.

ABSTRACT: Neutrophils migrating towards chemoattractant gradients amplify their recruitment range by releasing the secondary chemoattractant leukotriene B₄ (LTB₄) refs. ^1,2. We previously demonstrated that LTB₄ and its synthesizing enzymes, 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP) and leukotriene A₄ hydrolase, are packaged and released in exosomes³. Here we report that the biogenesis of the LTB₄-containing exosomes originates at the nuclear envelope (NE) of activated neutrophils. We show that the neutral sphingomyelinase 1 (nSMase1)-mediated generation of ceramide-enriched lipid-ordered microdomains initiates the clustering of the LTB₄-synthesizing enzymes on the NE. We isolated and analysed exosomes

SUBMITTER: Arya SB 

PROVIDER: S-EPMC10211458 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature