LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration

Ewa P. Wojcikiewicz, Rory R. Koenen, Line Fraemohs, Julia Minkiewicz, Hashem Azad, Christian Weber, Vincent T. Moy

Research output: Contribution to journalArticle

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Abstract

Leukocyte transendothelial migration into inflamed areas is regulated by the integrity of endothelial cell junctions and is stabilized by adhesion molecules including junctional adhesion molecule-A (JAM-A). JAM-A has been shown to participate in homophilic interactions with itself and in heterophilic interactions with leukocyte function-associated antigen-1 (LFA-1) via its first and second immunoglobulin domains, respectively. Using competitive binding assays in conjunction with atomic force microscopy adhesion measurements, we provide compelling evidence that the second domain of JAM-A stabilizes the homo-philic interaction because its deletion suppresses the dynamic strength of the JAM-A homophilic interaction. Moreover, binding of the LFA-1 inserted domain to the second domain of JAM-A reduces the dynamic strength of the JAM-A homophilic interaction to the level measured with the JAM-A domain 2 deletion mutant. This finding suggests that LFA-1 binding cancels the stabilizing effects of the second immunoglobulin domain of JAM-A. Finally, our atomic force microscopy measurements reveal that the interaction of JAM-A with LFA-1 is stronger than the JAM-A homophilic interaction. Taken together, these results suggest that LFA-1 binding to JAM-A destabilizes the JAM-A homophilic interaction. In turn, the greater strength of the LFA-1/JAM-A complex permits it to support the tension needed to disrupt the JAM-A homophilic interaction, thus allowing transendothelial migration to proceed.

Original languageEnglish
Pages (from-to)285-293
Number of pages9
JournalBiophysical Journal
Volume96
Issue number1
DOIs
StatePublished - Jan 7 2009

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Junctional Adhesion Molecule A
Lymphocyte Function-Associated Antigen-1
Leukocytes
Transendothelial and Transepithelial Migration
Atomic Force Microscopy
Competitive Binding
Intercellular Junctions

ASJC Scopus subject areas

  • Biophysics

Cite this

Wojcikiewicz, E. P., Koenen, R. R., Fraemohs, L., Minkiewicz, J., Azad, H., Weber, C., & Moy, V. T. (2009). LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration. Biophysical Journal, 96(1), 285-293. https://doi.org/10.1529/biophysj.108.135491

LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration. / Wojcikiewicz, Ewa P.; Koenen, Rory R.; Fraemohs, Line; Minkiewicz, Julia; Azad, Hashem; Weber, Christian; Moy, Vincent T.

In: Biophysical Journal, Vol. 96, No. 1, 07.01.2009, p. 285-293.

Research output: Contribution to journalArticle

Wojcikiewicz, EP, Koenen, RR, Fraemohs, L, Minkiewicz, J, Azad, H, Weber, C & Moy, VT 2009, 'LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration', Biophysical Journal, vol. 96, no. 1, pp. 285-293. https://doi.org/10.1529/biophysj.108.135491
Wojcikiewicz EP, Koenen RR, Fraemohs L, Minkiewicz J, Azad H, Weber C et al. LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration. Biophysical Journal. 2009 Jan 7;96(1):285-293. https://doi.org/10.1529/biophysj.108.135491
Wojcikiewicz, Ewa P. ; Koenen, Rory R. ; Fraemohs, Line ; Minkiewicz, Julia ; Azad, Hashem ; Weber, Christian ; Moy, Vincent T. / LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration. In: Biophysical Journal. 2009 ; Vol. 96, No. 1. pp. 285-293.
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