Role for phosphatidylinositol in nuclear envelope formation.
PtdIns is a minor membrane phospholipid that is important in signal transduction. Recently, derivatives of PtdIns phosphorylated at the 3-position of the inositol ring have been implicated in the regulation of constitutive membrane traffic and in membrane fusion events. Assembly of the nuclear envelope (NE), a crucial step in the progress of mitosis, is also likely to involve membrane fusion reactions. We therefore investigated the role of PtdIns and phosphoinositide 3-kinase (PI-3K) activity in NE formation in vitro. GTP-induced NE formation was blocked by wortmannin and LY294002, two specific inhibitors of PI-3K, suggesting a role for PtdIns phosphorylated at the 3-position. PtdIns-specific phospholipase C mimicked GTP hydrolysis as an inducer of NE formation. This induction was dependent on a membrane vesicle subfraction (MV1) that was highly enriched in PtdIns, as determined by heteronuclear two-dimensional NMR spectroscopy. On the basis of these results, we suggest that the MV1 population serves as a source of membranes rich in PtdIns that might facilitate fusion, possibly through the production of the membrane-destabilizing lipid diacylglycerol.
Larijani
B
B
Department of Biology, Amherst College, Amherst, MA 01002, USA. b.larijani@icrf.icnet.uk
Barona
T M
TM
Poccia
D L
DL
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008561:Membrane Fusion / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010743:Phospholipids / Q000378:metabolism; D012617:Sea Urchins; D010738:Type C Phospholipases / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D006160:Guanosine Triphosphate; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010743:Phospholipids; D010738:Type C Phospholipases; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one