A Single Aplysia Neurotrophin Mediates Synaptic Facilitation via Differentially Processed Isoforms
Stefan R. Kassabov,
Yun-Beom Choi,
Kevin A. Karl,
Harshad D. Vishwasrao,
Craig H. Bailey,
Eric R. Kandel
Affiliations
Stefan R. Kassabov
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032
Yun-Beom Choi
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032
Kevin A. Karl
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032
Harshad D. Vishwasrao
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032
Craig H. Bailey
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032
Eric R. Kandel
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032
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.
