A role for diacylglycerol in annexin A7-mediated fusion of lung lamellar bodies.
Lung surfactant secretion in alveolar type II cells occurs following lamellar body fusion with plasma membrane. Annexin A7 is a Ca2+-dependent membrane-binding protein that is postulated to promote membrane fusion during exocytosis in some cell types including type II cells. Since annexin A7 preferably binds to lamellar body membranes, we postulated that specific lipids could modify the mode of annexin A7 interaction with membranes and its membrane fusion activity. Initial studies with phospholipid vesicles containing phosphatidylserine and other lipids showed that certain lipids affected protein interaction with vesicle membranes as determined by change in protein tryptophan fluorescence, protein interaction with trans membranes, and by protein sensitivity to limited proteolysis. The presence of signaling lipids, diacylglycerol or phosphatidylinositol-4,5-bisphosphate, as minor components also modified the lipid vesicle effect on these characteristics and membrane fusion activity of annexin A7. In vitro incubation of lamellar bodies with diacylglycerol or phosphatidylinositol-4,5-bisphosphate caused their enrichment with either lipid, and increased the annexin A7 and Ca2+-mediated fusion of lamellar bodies. Treatment of isolated lung lamellar bodies with phosphatidylinositol- or phosphatidylcholine phospholipase C to increase diacylglycerol, without or with preincubation with phosphatidylinositol-4,5-bisphosphate, augmented the fusion activity of annexin A7. Thus, increased diacylglycerol in lamellar bodies following cell stimulation with secretagogues may enhance membrane fusion activity of annexin A7.
Chander
Avinash
A
Division of Neonatology and the Brady Laboratory, Department of Pediatrics, Stony Brook University Medical Center, Stony Brook, NY 11794, USA. ajerath@notes.cc.sunysb.edu
Chen
Xiao-Liang
XL
Naidu
Devendra G
DG
D000818:Animals; D017310:Annexin A7 / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003619:Dansyl Compounds / Q000737:chemistry; D004075:Diglycerides / Q000502:physiology*; D005786:Gene Expression Regulation; D008168:Lung / Q000378:metabolism*; D008297:Male; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry; D010738:Type C Phospholipases / Q000378:metabolism
D017310:Annexin A7; D003619:Dansyl Compounds; D004075:Diglycerides; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D013501:Surface-Active Agents; C024284:dansyl phosphatidylethanolamine; D014364:Tryptophan; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D002118:Calcium