Comodulation of CXCR4 and CD26 in human lymphocytes.
We provide convergent and multiple evidence for a CD26/CXCR4 interaction. Thus, CD26 codistributes with CXCR4, and both coimmunoprecipitate from membranes of T (CD4(+)) and B (CD4(-)) cell lines. Upon induction with stromal cell-derived factor 1alpha (SDF-1alpha), CD26 is cointernalized with CXCR4. CXCR4-mediated down-regulation of CD26 is not induced by antagonists or human immunodeficiency virus (HIV)-1 gp120. SDF-1alpha-mediated down-regulation of CD26 is not blocked by pertussis toxin but does not occur in cells expressing mutant CXCR4 receptors unable to internalize. Codistribution and cointernalization also occurs in peripheral blood lymphocytes. Since CD26 is a cell surface endopeptidase that has the capacity to cleave SDF-1alpha, the CXCR4.CD26 complex is likely a functional unit in which CD26 may directly modulate SDF-1alpha-induced chemotaxis and antiviral capacity. CD26 anchors adenosine deaminase (ADA) to the lymphocyte cell surface, and this interaction is blocked by HIV-1 gp120. Here we demonstrate that gp120 interacts with CD26 and that gp120-mediated disruption of ADA/CD26 interaction is a consequence of a first interaction of gp120 with a domain different from the ADA binding site. SDF-1alpha and gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 colocalize and in which ADA is not present. The physical association of CXCR4 and CD26, direct or part of a supramolecular structure, suggests a role on the function of the immune system and the pathophysiology of HIV infection.
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona, Marti i Franquès 1, 08028 Barcelona, Catalonia, Spain.
C
C
Herrera
C
C
Morimoto
J
J
Blanco
J
J
Mallol
F
F
Arenzana
C
C
Lluis
R
R
Franco
D000243:Adenosine Deaminase / Q000378:metabolism; D001665:Binding Sites; D015153:Blotting, Western; D015704:CD4 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D015536:Down-Regulation; D010450:Endopeptidases / Q000378:metabolism; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000378:metabolism*; D009154:Mutation; D037342:Pertussis Toxin; D011233:Precipitin Tests; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D010450:Endopeptidases; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase