Phosphatidylserine externalization and membrane blebbing are involved in the nonclassical export of FGF1.
The mechanisms of nonclassical export of signal peptide-less proteins remain insufficiently understood. Here, we demonstrate that stress-induced unconventional export of FGF1, a potent and ubiquitously expressed mitogenic and proangiogenic protein, is associated with and dependent on the formation of membrane blebs and localized cell surface exposure of phosphatidylserine (PS). In addition, we found that the differentiation of promonocytic cells results in massive FGF1 release, which also correlates with membrane blebbing and exposure of PS. These findings indicate that the externalization of acidic phospholipids could be used as a pharmacological target to regulate the availability of FGF1 in the organism.
Maine Medical Center Research Institute, Scarborough, Maine Medical Center, ME 04074, USA.
Aleksandr
A
Kirov
Huda
H
Al-Hashimi
Phil
P
Solomon
Courtney
C
Mazur
Philip E
PE
Thorpe
Peter J
PJ
Sims
Francesca
F
Tarantini
Thallapuranam K Suresh
TK
Kumar
Igor
I
Prudovsky
D000818:Animals; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D022081:Cell Surface Extensions / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010718:Phosphatidylserines / Q000032:analysis*; D049294:Phospholipid Transfer Proteins / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D013312:Stress, Physiological; D020298:U937 Cells
D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D016220:Fibroblast Growth Factor 1; D002118:Calcium