The Transmembrane Adaptor Protein SCIMP Facilitates Sustained Dectin-1 Signaling in Dendritic Cells.
Transmembrane adaptor proteins are molecules specialized in recruiting cytoplasmic proteins to the proximity of the cell membrane as part of the signal transduction process. A member of this family, SLP65/SLP76, Csk-interacting membrane protein (SCIMP), recruits a complex of SLP65/SLP76 and Grb2 adaptor proteins, known to be involved in the activation of PLCγ1/2, Ras, and other pathways. SCIMP expression is restricted to antigen-presenting cells. In a previous cell line-based study, it was shown that, in B cells, SCIMP contributes to the reverse signaling in the immunological synapse, downstream of MHCII glycoproteins. There it mainly facilitates the activation of ERK MAP kinases. However, its importance for MHCII glycoprotein-dependent ERK signaling in primary B cells has not been analyzed. Moreover, its role in macrophages and dendritic cells has remained largely unknown. Here we present the results of our analysis of SCIMP-deficient mice. In these mice, we did not observe any defects in B cell signaling and B cell-dependent responses. On the other hand, we found that, in dendritic cells and macrophages, SCIMP expression is up-regulated after exposure to GM-CSF or the Dectin-1 agonist zymosan. Moreover, we found that SCIMP is strongly phosphorylated after Dectin-1 stimulation and that it participates in signal transduction downstream of this important pattern recognition receptor. Our analysis of SCIMP-deficient dendritic cells revealed that SCIMP specifically contributes to sustaining long-term MAP kinase signaling and cytokine production downstream of Dectin-1 because of an increased expression and sustained phosphorylation lasting at least 24 h after signal initiation.
From the Laboratories of Leukocyte Signaling and.
Jarmila
J
Kralova
From the Laboratories of Leukocyte Signaling and.
Matej
M
Fabisik
Molecular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic and.
Jana
J
Pokorna
From the Laboratories of Leukocyte Signaling and.
Tereza
T
Skopcova
the Centre d'Immunophénomique, PHENOMIN-CIPHE, Aix Marseille Université UM2, INSERM US012, CNRS UMS3367, 13288 Marseille, France.
Bernard
B
Malissen
From the Laboratories of Leukocyte Signaling and tomas.brdicka@img.cas.cz.
Tomas
T
Brdicka
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism; D000099181:Dectin-1
D048868:Adaptor Proteins, Signal Transducing; D037181:Lectins, C-Type; D051966:Phospholipase C gamma; D000099181:Dectin-1; C117399:Plcg1 protein, mouse
Dectin-1; ERK; SCIMP; dendritic cell; innate immunity; p38; pattern recognition receptor (PRR); phosphotyrosine signaling; signal transduction