Defects in synapse structure and function precede motor neuron degeneration in Drosophila models of FUS-related ALS

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Mohammad ShahidullahIrwin B Levitan

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads invariably to fatal paralysis associated with motor neuron degeneration and muscular atrophy. One gene associated with ALS encodes the DNA/RNA-binding protein Fused in Sarcoma (FUS). There now exist two Drosophila models of ALS. In one, human FUS with ALS-causing mutations is expressed in fly motor neurons; in the other, the gene cabeza (caz), the fly homolog of FUS, is ablated. These FUS-ALS flies exhibit larval locomotor defects indicative of neuromuscular dysfunction and early death. The locus and site of initiation of this neuromuscular dysfunction remain unclear. We show here that in FUS-ALS flies, motor neuron cell bodies fire action potentials that propagate along the axon and voltage-dependent inward and outward currents in the cell bodies are indistinguishable in wild-type and FUS-ALS motor neurons. In marked contrast, the amplitude of synaptic currents evoked in the postsynaptic muscle cell is decreased by >80% in FUS-ALS larvae. Furthermore, the frequency but not unitary amplitude of spontaneous miniature synaptic currents is decreased dramatically in FUS-ALS flies, consistent with a change in quantal content but not quantal si...Continue Reading

References

Sep 18, 2003·Development·Miki FujiokaJames B Jaynes
Oct 3, 2003·Journal of Neurophysiology·Jason J KuoAlfons B A Kroese
Jan 23, 2004·Experimental Neurology·Lindsey R FischerJonathan D Glass
Jun 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Atsushi Ueda, Chun-Fang Wu
Mar 1, 2008·Science·Jemeen SreedharanChristopher E Shaw
Oct 24, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Brigitte van ZundertMark C Bellingham
Mar 24, 2009·Cell·Clotilde Lagier-Tourenne, Don W Cleveland
Apr 24, 2009·Current Opinion in Pharmacology·Luc Dupuis, Jean-Philippe Loeffler
Apr 14, 2011·Human Molecular Genetics·Nicholas A LansonUdai Bhan Pandey
Jul 5, 2011·Cold Spring Harbor Protocols·Richard Benton, Anupama Dahanukar
Sep 2, 2011·The Journal of Clinical Investigation·Ji-Wu WangBrian D McCabe
Nov 29, 2011·Neurobiology of Aging·Laetitia MiguelMagalie Lecourtois
Feb 22, 2012·Brain Research·Nicholas A Lanson, Udai Bhan Pandey
Mar 27, 2012·Brain Research·Magdalini PolymenidouGene W Yeo
Jan 25, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gary A B Armstrong, Pierre Drapeau
Jun 19, 2013·Human Molecular Genetics·Gary A B Armstrong, Pierre Drapeau

❮ Previous
Next ❯

Citations

Feb 27, 2014·Human Molecular Genetics·James B MachamerThomas E Lloyd
Jun 26, 2014·Neuroscience Bulletin·Epaminondas Doxakis
May 16, 2014·Genes·Radoslaw K Ejsmont, Bassem A Hassan
Apr 2, 2016·Brain Research·Yulei Shang, Eric J Huang
Jun 7, 2015·Cellular and Molecular Life Sciences : CMLS·Chantelle F Sephton, Gang Yu
Oct 8, 2014·Brain Research·Ian Casci, Udai Bhan Pandey
Sep 10, 2014·Molecular Neurobiology·Tyler B TarrStephen D Meriney
Jun 9, 2015·Frontiers in Cellular Neuroscience·Joseph J BrucknerKate M O'Connor-Giles
May 6, 2014·Current Opinion in Chemical Biology·Katrin I Willig, Francisco J Barrantes
Apr 28, 2016·Scientific Reports·Martine TherrienJ Alex Parker
Oct 30, 2016·RNA Biology·Francesca SvetoniMaria Paola Paronetto
Mar 5, 2016·Journal of Neurochemistry·Hilary A Bowden, Dorothee Dormann
Sep 17, 2016·The Journal of Physiology·Danielle ArbourRichard Robitaille
Mar 7, 2017·Chemical Reviews·Hans Blom, Jerker Widengren
Jan 4, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kirat K ChandPeter G Noakes
Dec 19, 2019·Brain : a Journal of Neurology·Virenkumar A Pandya, Rickie Patani
Apr 4, 2017·Human Molecular Genetics·Pei-Ying WangGuey-Shin Wang
Jun 18, 2017·Journal of Molecular Neuroscience : MN·Sonja Prpar MihevcTomaz Mars
Jul 28, 2018·Scientific Reports·Itaru YamamotoMasamitsu Yamaguchi
Dec 19, 2016·Frontiers in Cellular Neuroscience·Dante J HerediaThomas W Gould
May 15, 2019·Biology·Veronica Granatiero, Giovanni Manfredi
Jun 28, 2019·Frontiers in Cellular Neuroscience·Dhruva DeshpandeJens Michaelis
Sep 29, 2020·Frontiers in Molecular Neuroscience·Perrine CastetsMarkus A Rüegg
Jan 23, 2021·International Journal of Molecular Sciences·Sophie LayalleLaurent Soustelle
Mar 18, 2021·Journal of Neuroscience Research·Karthik Krishnamurthy, Piera Pasinelli
Jun 13, 2021·Neuroscience Letters·Elke BraemsLudo Van Den Bosch
Jul 30, 2021·Cellular and Molecular Life Sciences : CMLS·Francesco LiguoriCinzia Volonté

❮ Previous
Next ❯

Related Concepts

Related Feeds

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.