title: The effects of ER morphology on synaptic structure and function in Drosophila melanogaster.
abstract: Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-type Drosophila motor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 ortholog atl. atl or Rtnl1 loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss of atl causes age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior.
authors.affiliation: Department of BioSciences, Program in Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Summerville
authors.affiliation: Department of BioSciences, Program in Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Faust
authors.affiliation: Department of BioSciences, Program in Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Fan
authors.affiliation: CNR, Neuroscience Institute, 35121 Padova, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Pendin
authors.affiliation: E. Medea Scientific Institute, 31015 Conegliano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Daga
authors.affiliation: Department of BioSciences, Program in Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Formella
authors.affiliation: Department of BioSciences, Program in Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA stern@rice.edu mcnew@rice.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Stern
authors.affiliation: Department of BioSciences, Program in Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA stern@rice.edu mcnew@rice.edu.
authors.forename: James A
authors.identifier: http://orcid.org/0000-0001-8459-3664
authors.initials: JA
authors.lastname: McNew
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009046:Motor Neurons / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015398:Signal Transduction; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D013569:Synapses; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C112025:RTN2 protein, human; C440006:ATL1 protein, human; D019204:GTP-Binding Proteins
keywords: Atlastin; ER; Neuron; Reticulon