A juxta-membrane amino acid sequence of P-selectin glycoprotein ligand-1 is involved in moesin binding and ezrin/radixin/moesin-directed targeting at the trailing edge of migrating lymphocytes.
P-selectin glycoprotein ligand 1 (PSGL-1) is an adhesion receptor localized on the tips of microvilli that is involved in the rolling of neutrophils on activated endothelium. We found that PSGL-1 was concentrated at the uropod of chemokine-stimulated lymphoid cells. Dynamic fluorescence videomicroscopy analyses of migrating lymphocytes demonstrated that PSGL-1 and moesin redistributed towards the cellular uropod at the trailing edge of these cells, where activated ezrin/radixin/moesin (ERM) proteins were located. An eighteen amino acid sequence in the juxta-membrane region of the PSGL-1 cytoplasmic tail was found to be critical for uropod targeting and moesin binding. Substitution of S336, S348, and the basic cluster R337K338 by alanines within this region significantly impaired both moesin binding and PSGL-1 polarization. These results underline the role of moesin in the subcellular redistribution of PSGL-1 in lymphoid cells and make evident the importance of specific serine residues within the cytoplasmic tail of PSGL-1 for this process.
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
Juan M
JM
Serrador
Ana
A
Urzainqui
Jose L
JL
Alonso-Lebrero
J Román
JR
Cabrero
Maria C
MC
Montoya
Miguel
M
Vicente-Manzanares
María
M
Yáñez-Mó
Francisco
F
Sánchez-Madrid
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D000099149:Ezrin
D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000099149:Ezrin; C084882:P-selectin ligand protein; C071058:moesin; C071776:radixin