title: Comparative analyses of glycerotoxin expression unveil a novel structural organization of the bloodworm venom system.
abstract: We present the first molecular characterization of glycerotoxin (GLTx), a potent neurotoxin found in the venom of the bloodworm Glycera tridactyla (Glyceridae, Annelida). Within the animal kingdom, GLTx shows a unique mode of action as it can specifically up-regulate the activity of Cav2.2 channels (N-type) in a reversible manner. The lack of sequence information has so far hampered a detailed understanding of its mode of action.
  
  
  
  Our analyses reveal three ~3.8 kb GLTx full-length transcripts, show that GLTx represents a multigene family, and suggest it functions as a dimer. An integrative approach using transcriptomics, quantitative real-time PCR, in situ hybridization, and immunocytochemistry shows that GLTx is highly expressed exclusively in four pharyngeal lobes, a previously unrecognized part of the venom apparatus.
  
  
  
  Our results overturn a century old textbook view on the glycerid venom system, suggesting that it is anatomically and functionally much more complex than previously thought. The herein presented GLTx sequence information constitutes an important step towards the establishment of GLTx as a versatile tool to understand the mechanism of synaptic function, as well as the mode of action of this novel neurotoxin.
authors.affiliation: Institute of Biology - Molecular Evolution and Systematics of Animals, University of Leipzig, Talstraße 33, D-04103, Leipzig, Germany. sr.sandyrichter@gmail.com.|German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Deutscher Platz 5e, D-04103, Leipzig, Germany. sr.sandyrichter@gmail.com.|Department of Life Sciences, Natural History Museum, Cromwell Rd, London, SW7 5BD, UK. sr.sandyrichter@gmail.com.
authors.forename: Sandy
authors.initials: S
authors.lastname: Richter
authors.affiliation: Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgate 55, N-5008, Bergen, Norway.
authors.forename: Conrad
authors.initials: C
authors.lastname: Helm
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, University of Queensland, St. Lucia, Brisbane, 4072, QLD, Australia.
authors.forename: Frederic A
authors.initials: FA
authors.lastname: Meunier
authors.affiliation: Institute of Biology - Department of Zoology, University of Kassel, Heinrich-Plett-Straße 40, D-34132, Kassel, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Hering
authors.affiliation: Department of Life Sciences, Natural History Museum, Cromwell Rd, London, SW7 5BD, UK.|The European Bioinformatics Institute (EMBL-EBI) - Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
authors.forename: Lahcen I
authors.initials: LI
authors.lastname: Campbell
authors.affiliation: Institute of Biology - Molecular Evolution and Systematics of Animals, University of Leipzig, Talstraße 33, D-04103, Leipzig, Germany.
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Drukewitz
authors.affiliation: Centre for Advanced Imaging, University of Queensland, St. Lucia, Brisbane, 4072, QLD, Australia.
authors.forename: Eivind A B
authors.initials: EA
authors.lastname: Undheim
authors.affiliation: Department of Life Sciences, Natural History Museum, Cromwell Rd, London, SW7 5BD, UK.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Jenner
authors.affiliation: Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Schiavo
authors.affiliation: Institute of Biology - Molecular Evolution and Systematics of Animals, University of Leipzig, Talstraße 33, D-04103, Leipzig, Germany. christoph.bleidorn@gmail.com.|German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Deutscher Platz 5e, D-04103, Leipzig, Germany. christoph.bleidorn@gmail.com.|Museo Nacional de Ciencias Naturales, Spanish National Research Council (CSIC), Calle José Gutierrez Abascal 2, 28006, Madrid, Spain. christoph.bleidorn@gmail.com.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bleidorn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000845:Annelida / Q000235:genetics / Q000502:physiology*; D015801:Helminth Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D005810:Multigene Family; D009498:Neurotoxins / Q000096:biosynthesis* / Q000737:chemistry; D014688:Venoms / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics
chemical_list: D015801:Helminth Proteins; D009498:Neurotoxins; D014688:Venoms; C042564:glycerotoxin
keywords: Annelida; Calcium channel; GLTx; Glyceridae; Neurotoxin; Venom system