Developmental Regulation of Multidrug Efflux Transporter Activity in Echinoderm Embryos

HAMDOUN, Amro; HODIN, Jason; SMITAL, Tvrtko; EPEL, David; Hopkins Marine Station, Stanford University; Univeristy of Washington, Seattle; Rudjer Boskovic Institute, Croatia; Hopkins Marine Station, Stanford University: Developmental Regulation of Multidrug Efflux Transporter Activity in Echinoderm Embryos

Here we present a study of multidrug (mdr) efflux transporter activity during embryonic and larval development through metamorphosis in two Pacific echinoderms, purple sea urchins (Strongylocentrotus purpuratus) and sand dollars (Dendraster excentricus). Previous research has demonstrated the expression of mdr genes and mdr transporter activity in the egg and 2-cell sea urchin embryo. Using specific inhibitors of the different efflux transporters, mrps and pgps, we confirm that both species exhibit distinct mrp and p-gp-like transport phenotypes. Importantly p-gp and mrp inhibitors show additive effects, demonstrating that multiple efflux transporters are simultaneously active during development. Our results indicate shifts in relative transport activities at key life history transitions including fertilization, hatching, feeding and settlement. At all developmental stages sand dollars exhibit higher relative activities of p-gp activity than sea urchins. The levels of both transport activities are increased dramatically at fertilization in both species but in later development they are regulated independently in a species and cell-type specific fashion. We propose that regulation of multiple efflux transporters may be an adaptation to the different environments in which these embryos develop and the different endogenous roles these transporters play in the development of each species. We discuss future experiments to test this hypothesis in the context of a comparative study on mdr transporter physiology at comparable ontogenetic stages across echinoderm species.

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