Immune synapse formation requires ZAP-70 recruitment by ezrin and CD43 removal by moesin.
Immunological synapse (IS) formation involves receptor-ligand pair clustering and intracellular signaling molecule recruitment with a coincident removal of other membrane proteins away from the IS. As microfilament-membrane linkage is critical to this process, we investigated the involvement of ezrin and moesin, the two ezrin/radixin/moesin proteins expressed in T cells. We demonstrate that ezrin and moesin, which are generally believed to be functionally redundant, are differentially localized and have important and complementary functions in IS formation. Specifically, we find that ezrin directly interacts with and recruits the signaling kinase ZAP-70 to the IS. Furthermore, the activation of ezrin by phosphorylation is essential for this process. In contrast, moesin dephosphorylation and removal, along with CD43, are necessary to prepare a region of the cell cortex for IS. Thus, ezrin and moesin have distinct and critical functions in the T cell cortex during IS formation.
Ilani
Tal
T
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Khanna
Chand
C
Zhou
Ming
M
Veenstra
Timothy D
TD
Bretscher
Anthony
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051917:Leukosialin / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D010766:Phosphorylation; D011233:Precipitin Tests; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D014162:Transfection; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism / Q000502:physiology*; D000099149:Ezrin
D002118:Calcium; D003598:Cytoskeletal Proteins; D051917:Leukosialin; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D051746:ZAP-70 Protein-Tyrosine Kinase; D000099149:Ezrin; C071058:moesin; C497261:ZAP70 protein, human