title: Processing, axonal transport and cardioregulatory functions of peptides derived from two related prohormones generated by alternative splicing of a single gene in identified neurons VD1 and RPD2 of Lymnaea.
abstract: The VD1/RPD2 mRNA precursor in identified neurons VD1 and RPD2 of the freshwater snail Lymnaea stagnalis is alternatively spliced to yield two related variants encoding two distinct yet related preprohormones, named the VD1/RPD2-A and -B preprohormones. Here, we report the isolation and structural characterization of alpha 1, alpha 2 and beta peptides from dissected neurons VD1 and RPD2. The alpha 1 and alpha 2 peptides are derived from VD1/RPD2-A and B prohormones, respectively, whereas beta peptide is identical for both prohormones. In addition, we report the isolation and structural characterization of the alpha 2 peptide from the heart, demonstrating that the mature peptides are transported and released in the heart. The pharmacological actions of synthetic alpha 1 and alpha 2 peptides on isolated auricle preparations of the Lymnaea heart were examined. The two alpha peptides have similar excitatory effects on beat rate and beat amplitude, while their potencies differed considerably, indicating that alternative splicing results in structurally and functionally overlapping, through non-identical, sets of peptides.
authors.affiliation: Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Faculty of Biology, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Bogerd
authors.forename: K W
authors.initials: KW
authors.lastname: Li
authors.forename: C R
authors.initials: CR
authors.lastname: Jiménez
authors.forename: R C
authors.initials: RC
authors.lastname: van der Schors
authors.forename: R H
authors.initials: RH
authors.lastname: Ebberink
authors.forename: W P
authors.initials: WP
authors.lastname: Geraerts
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000737:chemistry; D001370:Axonal Transport; D001681:Biological Assay; D005796:Genes; D006339:Heart Rate / Q000187:drug effects; D007447:Invertebrate Hormones / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008195:Lymnaea / Q000166:cytology / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012326:RNA Splicing; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D007447:Invertebrate Hormones; D009479:Neuropeptides; D011498:Protein Precursors; C082583:VD1-RPD2 alpha preprohormone, Lymnaea; C088252:VD1-RPD2 neuropeptide alpha1; C072179:VD1-RPD2 neuropeptide beta; C088253:VD1-RPD2 neuropeptide alpha2