FERTILIZATION Starting Out with a New Second Messenger

Churchill et al. put the final piece into place to designate nicotinic acid adenine dinucleotide phosphate (NAADP) as a second messenger. Although the Ca²⁺-mobilizing agent NAADP fulfills many criteria for a second messenger, its concentration inside cells has never been shown to increase after a physiologically relevant stimulus. Churchill et al. investigated the role of NAADP in sea urchin egg fertilization. The authors used a radioreceptor assay to demonstrate a biphasic increase in NAADP in extracts of eggs and sperm after fertilization. An increase in NAADP similar in magnitude to the earlier peak occurred in sperm incubated with egg jelly, indicating that this increase was due to NAADP production in sperm. Fertilization depleted NAADP-sensitive Ca²⁺ stores in egg homogenates, but not Ca²⁺ stores mobilized by inositol-1,4,5-trisphosphate (IP₃) or cyclic adenosine diphosphate ribose (cADPR). Intra-oocyte photorelease of NAADP--but not IP₃, Ca²⁺, or cADPR--elicited an increase in Ca²⁺ throughout the egg cortex (a cortical flash) that depended on Ca²⁺ influx, as is seen after fertilization. Repeated release of NAADP led to desensitization of the NAADP-triggered cortical flash and also inhibited the cortical flash to fertilization. These data suggest that exposure to the egg elicits NAADP production by the sperm, which then introduces the NAADP into the egg, triggering the cortical flash. The increase in NAADP after fertilization, combined with the similarity in the response of the egg to NAADP to the sequelae of fertilization, establish NAADP as a bona fide second messenger in the sea urchin oocyte.

G. C. Churchill, J. S. O'Neill, R. Masgrau, S. Patel, J. M. Thomas, A. A. Genazzani, A. Galione, Sperm deliver a new second messenger: NAADP. Curr. Biol. 13, 125-128 (2003). [Online Journal]

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