SLAM is a microbial sensor which regulates bacterial phagosome functions in macrophages by recruiting a Vps34/beclin 1/UVRAG complex (112.8)

Abstract Phagocytosis is a pivotal process by which macrophages eliminate microorganisms upon recognition by pathogen sensors. Surprisingly, the self-ligand cell surface receptor Slamf1 functions not only as a co-stimulatory molecule but also as a microbial sensor controlling killing of Gram-negative bacteria by macrophages. Slamf1 regulates activity of the Nox2 enzyme and phagolysosomal maturation upon entering the phagosome, by recruiting the enzyme Vps34, which produces PI3P. Here we report that in mouse macrophages, Slamf1 interacted with Vps34, Beclin 1 and UVRAG in E. coli-containing phagosomes. However this interaction was also found without induction of phagocytosis in macrophages, transfectant HEK293 cells and human chronic lymphocytic leukemia cells. Removal of the second ITAM motif in the cytoplasmic tail of Slamf1 seemed to enhance the interaction of Slamf1 with Beclin 1, while Slamf1 tailless totally abolished the interaction. Both the BD and CCD domains of Beclin 1 were required for efficient binding to Slamf1. Slamf1 did not interact with Atg14L or Rubicon, which also complex with Vps34 and Beclin 1 in autophagy. We conclude that Slamf1 recruits a subset of Vps34 associated proteins, which is involved in membrane fusions.