Cells lacking glycan phosphatidylinositol-linked proteins have impaired ability to vesiculate.
Erythrocytes shed membrane vesicles in response to many stimuli. It has been previously demonstrated that glycan phosphatidylinositol-linked (GPI-linked) proteins such as decay accelerating factor and acetylcholinesterase are concentrated in these vesicles relative to the erythrocyte membrane. We have examined the requirement for GPI-linked proteins for the process of vesiculation. Erythrocytes that do not express GPI-linked proteins, obtained from patients with paroxysmal nocturnal hemoglobinuria (PNH), release between 10% and 50% of the quantity of vesicles as normal cells in response to the Ca2+ ionophore A23187. Platelets from the same patients produced 10% to 20% of the amount of vesicles as normal platelets. In addition, a mutant B-lymphoblastoid cell line that lacks GPI-linked molecules produces about half of the number of vesicles as compared with the wild-type cell line in response to the Ca2+ ionophore. Prior findings indicate that vesiculation is one of the mechanisms that the cell uses to remodel the plasma membrane, as well as protect itself from membrane-damaging agents such as the terminal complement components C5b-9. On the basis of the present results, we conclude that GPI-linked proteins play an important role in membrane vesiculation.
Whitlow
M
M
Dermatology Service, Department of Veterans Affairs Medical Center, New York.
Iida
K
K
Marshall
P
P
Silber
R
R
Nussenzweig
V
V
D000110:Acetylcholinesterase / Q000097:blood*; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D018958:CD55 Antigens; D018957:CD59 Antigens; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000097:blood*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000097:blood*; D008565:Membrane Proteins / Q000097:blood*; D012016:Reference Values
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001798:Blood Proteins; D018958:CD55 Antigens; D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000001:Calcimycin; D000110:Acetylcholinesterase; D002118:Calcium