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The mast cell: where endocytosis and regulated exocytosis meet


  • Ronit Sagi-Eisenberg

    Corresponding author
    1. Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Ronit Sagi-Eisenberg
Department of Cell and Developmental Biology
Sackler School of Medicine
Tel Aviv University
Tel Aviv 69978
Tel.: 972-3-640-9500
Fax: 972-3-640-7432


Summary:  We have investigated whether Ca2+-binding proteins, which have been implicated in the control of neurons and neuroendocrine secretion, play a role in controlling mast cell function. These studies have identified synaptotagmins (Syts) II, III, and IX as well as neuronal Ca2+ sensor 1 (NCS-1) as important regulators of mast cell function. Strikingly, we find that these Ca2+-binding proteins contribute to mast cell function by regulating specific endocytic pathways. Syt II, the most abundant Syt homologue in mast cells, resides in an amine-free lysosomal compartment. Studying the function of Syt II-knocked down rat basophilic leukemia cells has shown a dual function of this homologue. Syt II is required for the downregulation of protein kinase Cα, but it negatively regulates lysosomal exocytosis. Syt III, the next most abundant homologue, localizes to early endosomes and is required for the formation of the endocytic recycling compartment (ERC). Syt IX and NCS-1 localize to the ERC and regulate ERC export, NCS-1 by activating phosphatidylinositol 4-kinase β. Finally, we show that recycling through the ERC is needed for secretory granule protein sorting as well as for the activation of the mitogen-activated protein kinases, extracellular signal-regulated kinase 1 and 2. Accordingly, NCS-1 stimulates FcɛRI-triggered exocytosis and release of arachidonic acid metabolites.