Meeting Abstract

66.8  Friday, Jan. 6  Genome-wide Characterization of Signaling Peptides in Molluscs: Insights into Neuronal Evolution KOHN, A.B.*; CITARELLA, M.R.; GILLETTE, R.; SWEEDLER, J.V.; MOROZ, L.L.; Whitney Lab for Marine Bioscience University of Florida, St Augustine, FL; Whitney Lab for Marine Bioscience University of Florida, St Augustine, FL; Department of Chemistry and the Beckman Institute, University of Illinois at Urbana-Champaign, Urbana-Champaign, Illinois; Department of Chemistry and the Beckman Institute, University of Illinois at Urbana-Champaign, Urbana-Champaign, Illinois; Dept of Neuroscience,University of Florida, Gainesville, FL, Whitney Lab for Marine Bioscience University of Florida, St Augustine, FL abkohn@msn.com

Neuropeptides and protein hormones are ancient signaling molecules involved in virtually every activity of neural circuits and plasticity. First, using a combination of direct genome-wide transcriptional profiling of individual neurons, the entire CNS and developmental stages, we have identified and characterized the genomic organization of 96 prohormones in Aplysia including 56 previously unknown secretory products. Second, using in situ hybridization we validated neuron-specific expression of all discovered prohormones and showed cell-specificity in their expression. At least 5-6 prohormones were identified in key neurons of a simpler memory forming circuit. Third, we identified at least 20 neuropeptide-type prohormones differentially expressed during development of Aplysia. These data indicates that many peptides controlling early development can be recruited as signal molecules within adult nervous systems including learning and memory processes. Fourth, we employed various mass spectrometry protocols (MALDI TOF & LC MS/MS) to confirm the expressing of novel prohormones in both developmental stages and neuronal samples leading to direct experimental validation for the majority of novel prohormones with an astonishing diversity of >500 secretory products in Aplysia. Fifth, using deep transcriptome profiling (>5 million ESTs) from CNSs of 12 gastropod and cephalopod species we identify >70 of Aplysia prohormone homologs as evolutionary conserved precursors for multiple classes of signal molecules. The comparative analysis indicates that neuropeptides are amongst the fastest evolving intercellular signal molecules. Combined comparative and proteomic data from molluscs provides the unique opportunities to reconstruct of ancestral neuronal lineages, identify cell homologies across species and reveal trends in evolution within neural circuits.