title: Identification of a new neuropeptide precursor reveals a novel source of extrinsic modulation in the feeding system of Aplysia.
abstract: The Aplysia feeding system is advantageous for investigating the role of neuropeptides in behavioral plasticity. One family of Aplysia neuropeptides is the myomodulins (MMs), originally purified from one of the feeding muscles, the accessory radula closer (ARC). However, two MMs, MMc and MMe, are not encoded on the only known MM gene. Here, we identify MM gene 2 (MMG2), which encodes MMc and MMe and four new neuropeptides. We use matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to verify that these novel MMG2-derived peptides (MMG2-DPs), as well as MMc and MMe, are synthesized from the precursor. Using antibodies against the MMG2-DPs, we demonstrate that neuronal processes that stain for MMG2-DPs are found in the buccal ganglion, which contains the feeding network, and in the buccal musculature including the ARC muscle. Surprisingly, however, no immunostaining is observed in buccal neurons including the ARC motoneurons. In situ hybridization reveals only few MMG2-expressing neurons that are mostly located in the pedal ganglion. Using immunohistochemical and electrophysiological techniques, we demonstrate that some of these pedal neurons project to the buccal ganglion and are the likely source of the MMG2-DP innervation of the feeding network and musculature. We show that the MMG2-DPs are bioactive both centrally and peripherally: they bias egestive feeding programs toward ingestive ones, and they modulate ARC muscle contractions. The multiple actions of the MMG2-DPs suggest that these peptides play a broad role in behavioral plasticity and that the pedal-buccal projection neurons that express them are a novel source of extrinsic modulation of the feeding system of Aplysia.
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Proekt
authors.forename: Ferdinand S
authors.initials: FS
authors.lastname: Vilim
authors.forename: Vera
authors.initials: V
authors.lastname: Alexeeva
authors.forename: Vladimir
authors.initials: V
authors.lastname: Brezina
authors.forename: Allyson
authors.initials: A
authors.lastname: Friedman
authors.forename: Jian
authors.initials: J
authors.lastname: Jing
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Zhurov
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
authors.forename: Klaudiusz R
authors.initials: KR
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001048:Aplysia / Q000235:genetics* / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D017952:Ganglia, Invertebrate / Q000502:physiology; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics* / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics* / Q000502:physiology
chemical_list: D009479:Neuropeptides; D011498:Protein Precursors; C053302:myomodulin