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Activity-Dependent Regulation of Neurohormone Synthesis and Its Impact on Reproductive Behavior in Aplysia¹

Department of Physiology,³ David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1751 Department of Neurology and Neurosurgery,⁴ Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4

The bag cell neurons (BCNs) of the mollusk Aplysia californica provide a simple model system for investigating cellular and molecular events regulating synthesis and secretion of a reproductive neuropeptide and their impact on physiology and behavior. The BCNs secrete a large amount of egg-laying hormone (ELH) in response to an electrical afterdischarge. The afterdischarge also triggers cellular and molecular events leading to upregulation of ELH biosynthesis to replenish the supply of releasable hormone that was lost because of secretion. In the present review, we discuss signal-transduction events that link membrane excitability to ELH biosynthesis. We present evidence that the afterdischarge stimulates ELH synthesis by upregulating translation of ELH mRNA rather than by activating ELH gene transcription. This increase in ELH synthesis is accompanied by a decrease in total protein synthesis, suggesting that the synthetic machinery is being funneled selectively toward ELH. We also discuss work showing that afterdischarge-induced ELH synthesis uses a novel mechanism of translation initiation, one involving a switch from cap-dependent to cap-independent translation initiation that activates an internal ribosome entry site (IRES) located in the 5'-untranslated region of ELH mRNA. The IRES-regulated translation provides a unique cellular mechanism to selectively upregulate synthesis of a critical reproductive hormone at the expense of nonessential proteins.

¹ Supported by grants from the National Institutes of Health (grants NS 33548 and HD 28336) to N.L.W., the Whitehall Foundation (grant F98-35) to N.L.W., the Physiology Department at UCLA to N.L.W., and the Canadian Institute of Health Research (grant MOP-15121) to W.S.S.

² Correspondence: Nancy L. Wayne, Department of Physiology, 53-231 CHS, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave., Los Angeles, CA, 90095-1751. FAX: 310-206-5661; nwayne{at}mednet.ucla.edu

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