Differential role of the Ca(2+) sensor synaptotagmin VII in macrophages and dendritic cells

Synaptotagmin VII (Syt VII) is a Ca(2+) sensing molecule that regulates lysosomal exocytosis in several cell types. In macrophages (MØ), Syt VII is required for efficient uptake of large particle loads, by promoting the delivery of lysosomal membrane to phagocytic cups. Here we compare the phagocytic capacity of bone marrow-derived MØs and dendritic cells (DC), and show that the requirement for Syt VII correlates with the unique ability of MØs for continuous phagocytosis. In contrast to MØs, Syt VII(+/+) and Syt VII(-/-) immature DCs show similar levels of initial phagocytosis, followed by a marked decrease in particle uptake. [Ca(2+)](i) chelation and PI-3 kinase inhibition reduce particle uptake by MØs, but are markedly less inhibitory in DCs. Thus, immature DCs appear to lack the Syt VII, Ca(2+) and PI-3 kinase-dependent forms of phagocytosis that are present in MØs. Interestingly, expression of Syt VII is up-regulated during LPS-induced DC maturation, a stimulus that also induces Syt VII translocation from intracellular compartments to the plasma membrane. Syt VII(-/-) DCs show a delayed translocation of MHC class II to the cell surface during maturation, consistent with the possibility that Syt VII facilitates exocytosis and/or surface retention of molecules critical for antigen presentation.