Tumor suppressor menin is required for subunit-specific nAChR α5 transcription and nAChR-dependent presynaptic facilitation in cultured mouse hippocampal neurons

Scientific Reports
Angela GetzNaweed I Syed

Abstract

In the central nervous system (CNS), cholinergic transmission induces synaptic plasticity that is required for learning and memory. However, our understanding of the development and maintenance of cholinergic circuits is limited, as the factors regulating the expression and clustering of neuronal nicotinic acetylcholine receptors (nAChRs) remain poorly defined. Recent studies from our group have implicated calpain-dependent proteolytic fragments of menin, the product of the MEN1 tumor suppressor gene, in coordinating the transcription and synaptic clustering of nAChRs in invertebrate central neurons. Here, we sought to determine whether an analogous cholinergic mechanism underlies menin's synaptogenic function in the vertebrate CNS. Our data from mouse primary hippocampal cultures demonstrate that menin and its calpain-dependent C-terminal fragment (C-menin) regulate the subunit-specific transcription and synaptic clustering of neuronal nAChRs, respectively. MEN1 knockdown decreased nAChR α5 subunit expression, the clustering of α7 subunit-containing nAChRs at glutamatergic presynaptic terminals, and nicotine-induced presynaptic facilitation. Moreover, the number and function of glutamatergic synapses was unaffected by MEN1 kno...Continue Reading

References

Oct 26, 1992·Neuroscience Letters·D BertrandM Ballivet
Jul 26, 1996·The Journal of Biological Chemistry·F WangJ Lindstrom
Feb 1, 1997·Trends in Neurosciences·S Wonnacott
Apr 18, 1997·Science·S C ChandrasekharappaS J Marx
Mar 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·S C GuruS C Chandrasekharappa
Apr 15, 1999·Annual Review of Neuroscience·J R Sanes, J W Lichtman
May 26, 1999·Mammalian Genome : Official Journal of the International Mammalian Genome Society·S C GuruS C Chandrasekharappa
Jun 11, 2003·Nature Neuroscience·Camin DeanPeter Scheiffele
Oct 1, 2003·Journal of Molecular Biology·Maud FromagetMartine Cordier-Bussat
Jan 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michael J ParkerGuoping Feng
Aug 31, 2004·Human Molecular Genetics·Valeria BusyginaAllen E Bale
Jan 18, 2005·Pharmacology, Biochemistry, and Behavior·Michelle A Vincler, James C Eisenach
Feb 4, 2005·Metabolism: Clinical and Experimental·Hiroyasu YoshikawaValdemar Grill
Jul 28, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ana Garcia-OstaCristina M Alberini
Oct 20, 2006·Molecular Cancer Research : MCR·Laura E MacConaillMatthew Meyerson
Apr 2, 2008·Journal of Neuropathology and Experimental Neurology·Changiz GeulaChuang-Kuo Wu
May 7, 2008·The Journal of Cell Biology·Melissa L HancockDavid A Talmage
Sep 12, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chongbo ZhongLorna W Role
Aug 5, 2009·Molecular and Cellular Biology·Yanan CaoGuang Ning
Apr 7, 2010·Cellular and Molecular Neurobiology·Xiaoqin ZhangBuwei Yu
Apr 21, 2010·The Journal of Biological Chemistry·Ting WuXianxin Hua
Jul 2, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nolan R CampbellDarwin K Berg
Jun 1, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Adrian F LozadaDarwin K Berg
Dec 21, 2012·Nature Reviews. Neuroscience·Hyungju Park, Mu-ming Poo

❮ Previous
Next ❯

Methods Mentioned

BETA
dissection
fluorescence microscopy
PCR
Conical

Software Mentioned

NIS Elements
MiniAnalysis
ImageJ
SPSS Statistics
Odyssey
REST

Related Concepts

Related Feeds

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.