JAM-A promotes neutrophil chemotaxis by controlling integrin internalization and recycling

Maria Rosaria Cera, Monica Fabbri, Cinzia Molendini, Monica Corada, Fabrizio Orsenigo, Markus Rehberg, Christoph A. Reichel, Fritz Krombach, Ruggero Pardi, Elisabetta Dejana

Research output: Contribution to journalArticlepeer-review


The membrane-associated adhesion molecule JAM-A is required for neutrophil infiltration in inflammatory or ischemic tissues. JAM-A expressed in both endothelial cells and neutrophils has such a role, but the mechanism of action remains elusive. Here we show that JAM-A has a cell-autonomous role in neutrophil chemotaxis both in vivo and in vitro, which is independent of the interaction of neutrophils with endothelial cells. On activated neutrophils, JAM-A concentrates in a polarized fashion at the leading edge and uropod. Surprisingly, a significant amount of this protein is internalized in intracellular endosomal-like vesicles where it codistributes with integrin β1. Clustering of β1 integrin leads to JAM-A co-clustering, whereas clustering of JAM-A does not induce integrin association. Neutrophils derived from JAM-A-null mice are unable to correctly internalize β1 integrins upon chemotactic stimuli and this causes impaired uropod retraction and cell motility. Consistently, inhibition of integrin internalization upon treatment with BAPTA-AM induces a comparable phenotype. These data indicate that JAM-A is required for the correct internalization and recycling of integrins during cell migration and might explain why, in its absence, the directional migration of neutrophils towards an inflammatory stimulus is markedly impaired.

Original languageEnglish
Pages (from-to)268-277
Number of pages10
JournalJournal of Cell Science
Issue number2
Publication statusPublished - Jan 15 2009


  • Chemotaxis
  • Integrins
  • JAM
  • Leukocyte

ASJC Scopus subject areas

  • Cell Biology


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