title: Two proteolytic fragments of menin coordinate the nuclear transcription and postsynaptic clustering of neurotransmitter receptors during synaptogenesis between Lymnaea neurons.
abstract: Synapse formation and plasticity depend on nuclear transcription and site-specific protein targeting, but the molecular mechanisms that coordinate these steps have not been well defined. The MEN1 tumor suppressor gene, which encodes the protein menin, is known to induce synapse formation and plasticity in the CNS. This synaptogenic function has been conserved across evolution, however the underlying molecular mechanisms remain unidentified. Here, using central neurons from the invertebrate Lymnaea stagnalis, we demonstrate that menin coordinates subunit-specific transcriptional regulation and synaptic clustering of nicotinic acetylcholine receptors (nAChR) during neurotrophic factor (NTF)-dependent excitatory synaptogenesis, via two proteolytic fragments generated by calpain cleavage. Whereas menin is largely regarded as a nuclear protein, our data demonstrate a novel cytoplasmic function at central synapses. Furthermore, this study identifies a novel synaptogenic mechanism in which a single gene product coordinates the nuclear transcription and postsynaptic targeting of neurotransmitter receptors through distinct molecular functions of differentially localized proteolytic fragments.
authors.affiliation: Department of Cell Biology &Anatomy, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.|Department of Neuroscience, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Getz
authors.affiliation: Department of Physiology &Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Visser
authors.affiliation: Department of Cell Biology &Anatomy, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Bell
authors.affiliation: Department of Physiology &Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.|Department of Biology, Saint Louis University, Saint Louis, Missouri, 63103, USA.
authors.forename: Fenglian
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Cell Biology &Anatomy, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.|Department of Neuroscience, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Nichole M
authors.initials: NM
authors.lastname: Flynn
authors.affiliation: Department of Cell Biology &Anatomy, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Wali
authors.initials: W
authors.lastname: Zaidi
authors.affiliation: Department of Cell Biology &Anatomy, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Naweed I
authors.initials: NI
authors.lastname: Syed
mesh_terms: D000818:Animals; D008195:Lymnaea / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000235:genetics; D013569:Synapses / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D011518:Proto-Oncogene Proteins; D017981:Receptors, Neurotransmitter