title: A single Aplysia neurotrophin mediates synaptic facilitation via differentially processed isoforms.
abstract: Neurotrophins control the development and adult plasticity of the vertebrate nervous system. Failure to identify invertebrate neurotrophin orthologs, however, has precluded studies in invertebrate models, limiting our understanding of fundamental aspects of neurotrophin biology and function. We identified a neurotrophin (ApNT) and Trk receptor (ApTrk) in the mollusk Aplysia and found that they play a central role in learning-related synaptic plasticity. Blocking ApTrk signaling impairs long-term facilitation, whereas augmenting ApNT expression enhances it and induces the growth of new synaptic varicosities at the monosynaptic connection between sensory and motor neurons of the gill-withdrawal reflex. Unlike vertebrate neurotrophins, ApNT has multiple coding exons and exerts distinct synaptic effects through differentially processed and secreted splice isoforms. Our findings demonstrate the existence of bona fide neurotrophin signaling in invertebrates and reveal a posttranscriptional mechanism that regulates neurotrophin processing and the release of proneurotrophins and mature neurotrophins that differentially modulate synaptic plasticity.
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. srk2110@columbia.edu
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Kassabov
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Choi
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Karl
authors.forename: Harshad D
authors.initials: HD
authors.lastname: Vishwasrao
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bailey
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity; D016716:PC12 Cells; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020917:Receptor, trkA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020033:Protein Isoforms; D012701:Serotonin; D020917:Receptor, trkA
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