title: Initial characterization of a Syap1 knock-out mouse and distribution of Syap1 in mouse brain and cultured motoneurons.
abstract: Synapse-associated protein 1 (Syap1/BSTA) is the mammalian homologue of Sap47 (synapse-associated protein of 47 kDa) in Drosophila. Sap47 null mutant larvae show reduced short-term synaptic plasticity and a defect in associative behavioral plasticity. In cultured adipocytes, Syap1 functions as part of a complex that phosphorylates protein kinase Bα/Akt1 (Akt1) at Ser(473) and promotes differentiation. The role of Syap1 in the vertebrate nervous system is unknown. Here, we generated a Syap1 knock-out mouse and show that lack of Syap1 is compatible with viability and fertility. Adult knock-out mice show no overt defects in brain morphology. In wild-type brain, Syap1 is found widely distributed in synaptic neuropil, notably in regions rich in glutamatergic synapses, but also in perinuclear structures associated with the Golgi apparatus of specific groups of neuronal cell bodies. In cultured motoneurons, Syap1 is located in axons and growth cones and is enriched in a perinuclear region partially overlapping with Golgi markers. We studied in detail the influence of Syap1 knockdown and knockout on structure and development of these cells. Importantly, Syap1 knockout does not affect motoneuron survival or axon growth. Unexpectedly, neither knockdown nor knockout of Syap1 in cultured motoneurons is associated with reduced Ser(473) or Thr(308) phosphorylation of Akt. Our findings demonstrate a widespread expression of Syap1 in the mouse central nervous system with regionally specific distribution patterns as illustrated in particular for olfactory bulb, hippocampus, and cerebellum.
authors.affiliation: Institute of Clinical Neurobiology, University of Würzburg, Versbacher Str. 5, 97078, Würzburg, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Schmitt
authors.affiliation: Institute of Clinical Neurobiology, University of Würzburg, Versbacher Str. 5, 97078, Würzburg, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Funk
authors.affiliation: Institute of Clinical Neurobiology, University of Würzburg, Versbacher Str. 5, 97078, Würzburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Blum
authors.affiliation: Institute of Anatomy and Cell Biology, University of Würzburg, 97070, Würzburg, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Asan
authors.affiliation: Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, 1210, Vienna, Austria.
authors.forename: Lill
authors.initials: L
authors.lastname: Andersen
authors.affiliation: Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, 1210, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rülicke
authors.affiliation: Institute of Clinical Neurobiology, University of Würzburg, Versbacher Str. 5, 97078, Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
authors.affiliation: Institute of Clinical Neurobiology, University of Würzburg, Versbacher Str. 5, 97078, Würzburg, Germany. Buchner_E@ukw.de.
authors.forename: Erich
authors.identifier: http://orcid.org/0000-0003-3031-8936
authors.initials: E
authors.lastname: Buchner
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C000620952:Syap1 protein, mouse
keywords: BSTA; Brain; Glutamatergic synapses; PKB/Akt phosphorylation; Syap1 localization; Viability