MON1 Homolog A (MON1A)

In worms deficient in either sand1 or ccz1, apoptotic cells were internalized and the phagosomes recruited the small GTPase Rab5 but failed to progress to the subsequent Rab7-positive stage. The mammalian orthologs of SAND1, namely MON1A and MON1B, were similarly required for phagosome maturation. Mechanistically, Mon1 interacts with GTP-bound Rab5, identifying Mon1 as a previously unrecognized Rab5 effector. Moreover, a Mon1-Ccz1 complex (but neither protein alone) could bind Rab7 and could also influence Rab7 activation, suggesting Mon1-Ccz1 as an important link in progression from the Rab5-positive stage to the Rab7-positive stage of phagosome maturation. These data identified SAND1 and CCZ1 as critical and evolutionarily conserved components regulating the processing of ingested apoptotic cell corpses.