title: Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1.
abstract: Galectin-1 induces apoptosis of human thymocytes and activated T cells by an unknown mechanism. Apoptosis is a novel function for a mammalian lectin; moreover, given the ubiquitous distribution of the oligosaccharide ligand recognized by galectin-1, it is not clear how susceptibility to and signaling by galectin-1 is regulated. We have determined that galectin-1 binds to a restricted set of T cell surface glycoproteins, and that only CD45, CD43, and CD7 appear to directly participate in galectin-1-induced apoptosis. To determine whether these specific glycoproteins interact cooperatively or independently to deliver the galectin-1 death signal, we examined the cell surface localization of CD45, CD43, CD7, and CD3 after galectin-1 binding to human T cell lines and human thymocytes. We found that galectin-1 binding resulted in a dramatic redistribution of these glycoproteins into segregated membrane microdomains on the cell surface. CD45 and CD3 colocalized on large islands on apoptotic blebs protruding from the cell surface. These islands also included externalized phosphatidylserine. In addition, the exposure of phosphatidylserine on the surface of galectin-1-treated cells occurred very rapidly. CD7 and CD43 colocalized in small patches away from the membrane blebs, which excluded externalized phosphatidylserine. Receptor segregation was not seen on cells that did not die in response to galectin-1, including mature thymocytes, suggesting that spatial redistribution of receptors into specific microdomains is required for triggering apoptosis.
authors.affiliation: Department of Pathology, University of California, Los Angeles, School of Medicine 90095, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Pace
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: P L
authors.initials: PL
authors.lastname: Stewart
authors.forename: L G
authors.initials: LG
authors.lastname: Baum
mesh_terms: D015703:Antigens, CD; D019011:Antigens, CD7 / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D037483:Galectin 1; D006388:Hemagglutinins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051917:Leukosialin; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D011940:Receptor Aggregation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D019011:Antigens, CD7; D037483:Galectin 1; D006388:Hemagglutinins; D051917:Leukosialin; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D010718:Phosphatidylserines; D011948:Receptors, Antigen, T-Cell; C465014:SPN protein, human; D012795:Sialoglycoproteins; D017493:Leukocyte Common Antigens