Signaling through CD43 regulates CD4 T-cell trafficking.
The mucin-like protein CD43 is excluded from the immune synapse, and regulates T-cell proliferation as well as T-cell migration. While the CD43 cytoplasmic domain is necessary for regulation of T-cell activation and proliferation, the mechanism via which CD43 regulates trafficking is not well defined. To investigate whether CD43 phosphorylation regulates its function in T cells, we used tandem mass spectrometry and identified Ser76 in murine CD43 as a previously unidentified site of basal phosphorylation. Interestingly, mutation of this single serine to alanine greatly diminishes T-cell trafficking to the lymph node, while CD43 exclusion and CD43-mediated regulation of T-cell proliferation remain intact. Furthermore, the CD43 extracellular domain was also required for T-cell trafficking, providing a hitherto unknown function for the extracellular domain, and suggesting that the extracellular domain may be required to transduce signals via the cytoplasmic domain. These data reveal a novel mechanism by which CD43 regulates T-cell function, and suggest that CD43 functions as a signaling molecule, sensing extracellular cues and transducing intracellular signals that modulate T-cell function.
Mody
Purvi D
PD
Committee on Immunology, University of Chicago, IL 60637, USA.
Cannon
Judy L
JL
Bandukwala
Hozefa S
HS
Blaine
Kelly M
KM
Schilling
Alexander B
AB
Swier
Kevin
K
Sperling
Anne I
AI
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology*; D017124:Conserved Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D051917:Leukosialin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D053719:Tandem Mass Spectrometry; D014161:Transduction, Genetic
D051917:Leukosialin