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Updated: Aug 9, 2026
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
LFA-1-dependent lipid raft recruitment of DNAM-1 (CD226) in CD4+ T cell
Jun Shirakawa1, Yinan Wang, Satoko Tahara-Hanaoka
1Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences and Center for TARA, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Insights
Leukocyte function-associated antigen-1 (LFA-1) is crucial for DNAM-1
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Leukocyte adhesion molecules DNAM-1 and LFA-1 cluster at the immunological synapse upon T-cell receptor (TCR) activation.
- DNAM-1's serine residue facilitates its lipid raft association and interaction with LFA-1.
- The precise mechanism linking serine phosphorylation to DNAM-1's lipid raft recruitment remained unclear.
Purpose of the Study:
- To elucidate the role of LFA-1 in the lipid raft recruitment of DNAM-1.
- To clarify the mechanism by which TCR signaling influences DNAM-1 localization.
Main Methods:
- Analysis of CD4+ T cells from LFA-1 deficient mice.
- Assessment of DNAM-1 serine phosphorylation upon TCR stimulation.
- Investigation of DNAM-1 association with lipid rafts.
Main Results:
- TCR-mediated signaling induced serine phosphorylation of DNAM-1.
- DNAM-1 failed to associate with lipid rafts in CD4+ T cells lacking LFA-1.
- DNAM-1 lipid raft recruitment was dependent on LFA-1 expression.
Conclusions:
- Serine phosphorylation of DNAM-1 promotes its physical association with LFA-1.
- LFA-1 acts as the key mediator for recruiting DNAM-1 into lipid rafts.
- This LFA-1-dependent mechanism is essential for DNAM-1 localization at the immunological synapse.
Abstract:
Upon antigen recognition by the TCR, both the leukocyte adhesion molecules DNAM-1 and leukocyte function-associated antigen-1 (LFA-1) associate with lipid rafts and form peripheral supra-molecular activation clusters that surround central-supra-molecular activation clusters at the immunological synapse. The serine residue in the cytoplasmic tail of DNAM-1 is responsible for this association of DNAM-1 with lipid rafts. The TCR-mediated signal also induces physical association of DNAM-1 with LFA-1, for which the serine phosphorylation of DNAM-1 is also responsible. However, how the serine residue is involved in lipid raft recruitment of DNAM-1 has remained unclear. Here, we show that, although the TCR-mediated signal induced the serine phosphorylation of DNAM-1, DNAM-1 did not associate with lipid rafts in CD4+ T cells derived from mice deficient in LFA-1 expression, indicating that lipid raft recruitment of DNAM-1 depends on LFA-1 expression. These results suggest that the serine phosphorylation of DNAM-1 primarily induces physical association of DNAM-1 with LFA-1, which then takes DNAM-1 into lipid raft compartment.
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