title: Tricornered Kinase Regulates Synapse Development by Regulating the Levels of Wiskott-Aldrich Syndrome Protein.
abstract: Precise regulation of synapses during development is essential to ensure accurate neural connectivity and function of nervous system. Many signaling pathways, including the mTOR (mechanical Target of Rapamycin) pathway operate in neurons to maintain genetically determined number of synapses during development. mTOR, a kinase, is shared between two functionally distinct multi-protein complexes- mTORC1 and mTORC2, that act downstream of Tuberous Sclerosis Complex (TSC). We and others have suggested an important role for TSC in synapse development at the Drosophila neuromuscular junction (NMJ) synapses. In addition, our data suggested that the regulation of the NMJ synapse numbers in Drosophila largely depends on signaling via mTORC2. In the present study, we further this observation by identifying Tricornered (Trc) kinase, a serine/threonine kinase as a likely mediator of TSC signaling. trc genetically interacts with Tsc2 to regulate the number of synapses. In addition, Tsc2 and trc mutants exhibit a dramatic reduction in synaptic levels of WASP, an important regulator of actin polymerization. We show that Trc regulates the WASP levels largely, by regulating the transcription of WASP. Finally, we show that overexpression of WASP (Wiskott-Aldrich Syndrome Protein) in trc mutants can suppress the increase in the number of synapses observed in trc mutants, suggesting that WASP regulates synapses downstream of Trc. Thus, our data provide a novel insight into how Trc may regulate the genetic program that controls the number of synapses during development.
authors.affiliation: Department of Neurology and Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Rajalaxmi
authors.initials: R
authors.lastname: Natarajan
authors.affiliation: Neuroscience Graduate Program, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Kara
authors.initials: K
authors.lastname: Barber
authors.affiliation: Department of Neurology and Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Buckley
authors.affiliation: Summer Undergraduate Research Program, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Phillip
authors.initials: P
authors.lastname: Cho
authors.affiliation: Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America; Neuroscience Graduate Program, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Anuoluwapo
authors.initials: A
authors.lastname: Egbejimi
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Neurology and Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Yogesh P
authors.initials: YP
authors.lastname: Wairkar
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D000076225:Mechanistic Target of Rapamycin Complex 2; D018613:Microscopy, Confocal; D008957:Models, Genetic; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000235:genetics* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C409633:HIW protein, Drosophila; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C515347:TSC1 protein, Drosophila; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C117726:gig protein, Drosophila; C419769:trc protein, Drosophila; D000076225:Mechanistic Target of Rapamycin Complex 2; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases