Calcium-sensing receptors signal constitutive macropinocytosis and facilitate the uptake of NOD2 ligands in macrophages

• DOI: 10.1038/ncomms11284
• Publication Date: 2016-04-06T09:29:31Z
• Authors: Johnathan Canton; Daniel Schlam; Christian Breuer; Michael Gütschow; Michael Glogauer; Sergio Grinstein
• Keywords: Pinocytosis; Calcium Signaling

Abstract Macropinocytosis can be induced in several cell types by stimulation with growth factors. In selected types, notably macrophages and dendritic cells, macropinocytosis occurs constitutively, supporting the uptake of antigens for subsequent presentation. Despite their different mode initiation contrasting physiological roles, it is tacitly assumed that both are mechanistically identical. We report constitutive stringently calcium dependent, while stimulus-induced not. Extracellular sensed G-protein-coupled calcium-sensing receptors (CaSR) signal through Gα-, phosphatidylinositol 3-kinase phospholipase C. These pathways promote recruitment exchange factors stimulate Rac and/or Cdc42, driving actin-dependent formation ruffles macropinosomes. addition, heterologous expression CaSR HEK293 cells confers on them ability to perform macropinocytosis. Finally, we show CaSR-induced facilitates sentinel function macrophages, promoting efficient delivery ligands cytosolic pattern-recognition receptors.