Polyisoprenyl phosphate signaling: Topography in human neutrophils

To determine the relationship of polyisoprenyl phosphate (PIPP) remodeling and signaling to the activation state of human neutrophils (PMN), we examin ed the impact of leukotriene B-4 (LTB4) on the conversion of a unique bioac tive isoprenoid (presqualene diphosphate: PSDP), recently identified as a n ovel endogenous signaling molecule. LTB4 initiated rapid decrements in tota l PSDP that were concurrent with the respiratory burst (e.g., O-2(-) format ion). PSDP was identified in nuclear (39%)-, granule (36%)-, and plasma mem brane (16%)-containing fractions of PMN. LTB4 receptor (BLT) activation led to a decrease in nuclear PSDP and concomitant increase in granule-associat ed PSDP. In addition, PMN nuclei displayed PSDP associated with chromatin a s established by mass spectrometry, Together, these results indicate that P SDP is present in membranes and receptor activation rapidly initiates subce llular PIPP remodeling (i.e., conversion) and distribution predominantly to granule membranes. Moreover, identification of nuclear PSDP provides the b asis for novel roles for PIPP and PSDP in nuclear-associated signaling even ts. (C) 2000 Academic Press.