Endosymbiotic association of the Symbiodinium dinoflagellates (zooxanthellae) with their cnidarian host cells involves an alteration in The development of the alga-enclosing phagosomes. To uncover its molecular basis, we previously investigated and established that the intracellular persistence of the zooxanthella-containing phagosomes involves specific alga-mediated interference with the expression of ApRab5 and ApRab7, two key endocytic regulatory Rab proteins, which results in the selective retention of the former on and exclusion of the later from the organelles. Here we examined the role of ApRab11, a cnidarian homologue of the key endocytic recycling regulator, Rab 11, in the Aiptasia-Symbiodinium endosymbiosis. ApRab11 protein shared 88% overall sequence identity with human Rab11A and contained all Rab-specific signature motifs. Co-localization and mutagenesis studies showed that EGFP-tagged ApRabl I was predominantly associated with recycling endosomes and functioned in the recycling of internalized transferrin. In phagocytosis of latex beads, ApRabl I was quickly recruited to and later gradually removed from the developing phagosomes. Significantly, although ApRab11 immunoreactivity was rapidly detected on the phagosomes containing either newly internalized, heat-killed zooxanthellae, or resident zooxanthellae briefly treated with the photosynthesis inhibitor DCMU, it was rarely observed in the majority of phagosomes containing either newly internalized live, or healthy resident, zooxanthellae. It was concluded that through active exclusion of ApRab11 from the phagosomes in which they reside, zooxanthellae interfere with the normal recycling process required for efficient phagosome maturation, and thereby, Secure their intracellular persistence, and consequently their endosymbiotic relationship with their cnidarian hosts. (c) 2005 Elsevier Inc. All rights reserved.