Tricornered Kinase Regulates Synapse Development by Regulating the Levels of Wiskott-Aldrich Syndrome Protein.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Drosophila Proteins/*genetics ; Protein Serine-Threonine Kinases/*genetics ; Synapses/*genetics ; Wiskott-Aldrich Syndrome Protein/*genetics; Animals ; Animals, Genetically Modified ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/growth & development ; Drosophila melanogaster/metabolism ; Epistasis, Genetic ; Gene Expression Regulation, Developmental ; Mechanistic Target of Rapamycin Complex 2 ; Microscopy, Confocal ; Models, Genetic ; Multiprotein Complexes/genetics ; Multiprotein Complexes/metabolism ; Mutation ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuromuscular Junction/genetics ; Neuromuscular Junction/metabolism ; Protein Serine-Threonine Kinases/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/genetics ; Synapses/metabolism ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Wiskott-Aldrich Syndrome Protein/metabolism

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.

Neuron. 2014 Sep 3;83(5):1131-43. (PMID: 25155956)
Trends Mol Med. 2007 Aug;13(8):319-26. (PMID: 17632034)
Nat Neurosci. 2005 Dec;8(12):1727-34. (PMID: 16286931)
Hum Mol Genet. 2013 May 15;22(10):2010-23. (PMID: 23393158)
Annu Rev Neurosci. 2005;28:25-55. (PMID: 16029114)
Neuroscience. 2013 Oct 22;251:90-107. (PMID: 22546337)
Nature. 2012 Aug 30;488(7413):647-51. (PMID: 22763451)
Ann Neurol. 2007 Feb;61(2):139-52. (PMID: 17279540)
PLoS Biol. 2010 Jun 08;8(6):e1000393. (PMID: 20543991)
Nat Cell Biol. 2003 Oct;5(10):914-20. (PMID: 14502294)
Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11211-6. (PMID: 22736793)
Neuron. 1996 Oct;17(4):627-40. (PMID: 8893021)
Mol Biol Cell. 2005 Feb;16(2):689-700. (PMID: 15591127)
Cell. 2012 Apr 13;149(2):274-93. (PMID: 22500797)
Neuron. 2009 Jul 30;63(2):203-15. (PMID: 19640479)
J Child Neurol. 2004 Sep;19(9):675-9. (PMID: 15563013)
J Neurosci. 2014 Mar 26;34(13):4466-80. (PMID: 24671993)
Hum Mol Genet. 2013 Jan 1;22(1):140-52. (PMID: 23049074)
Biochim Biophys Acta. 2008 Jan;1784(1):3-15. (PMID: 17881309)
Cell. 2006 Sep 8;126(5):955-68. (PMID: 16959574)
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17379-84. (PMID: 20844206)
Nat Rev Mol Cell Biol. 2006 Apr;7(4):253-64. (PMID: 16607288)
J Biochem. 2003 Sep;134(3):309-13. (PMID: 14561714)
Biochim Biophys Acta. 2013 Dec;1832(12):2257-63. (PMID: 24012719)
Semin Cell Dev Biol. 2012 Sep;23(7):770-84. (PMID: 22898666)
Neuron. 2006 Mar 16;49(6):833-44. (PMID: 16543132)
Exp Cell Res. 2010 Nov 1;316(18):3007-13. (PMID: 20580706)
Dev Biol. 2010 May 15;341(2):360-74. (PMID: 20211163)
J Cell Biol. 2010 Nov 1;191(3):661-75. (PMID: 21041451)
Genetics. 2000 Dec;156(4):1817-28. (PMID: 11102376)
Neuron. 2005 Sep 1;47(5):695-708. (PMID: 16129399)
Curr Opin Neurobiol. 2012 Oct;22(5):866-72. (PMID: 22440525)
Genetics. 2009 Aug;182(4):1089-100. (PMID: 19487563)
Cell. 2001 Nov 30;107(5):591-603. (PMID: 11733059)
Genetics. 2013 Nov;195(3):915-26. (PMID: 23979583)
Curr Opin Neurobiol. 2009 Apr;19(2):231-4. (PMID: 19545994)
J Neurogenet. 1994 Jul;9(3):157-76. (PMID: 7965385)
Neuron. 1994 Oct;13(4):823-35. (PMID: 7946331)
Neuron. 2012 Mar 22;73(6):1127-42. (PMID: 22445341)
Trends Neurosci. 2004 Mar;27(3):143-7. (PMID: 15036879)
J Cell Sci. 2009 Aug 1;122(Pt 15):2575-8. (PMID: 19625501)
Mol Biol Cell. 2005 Sep;16(9):4139-52. (PMID: 15975907)
J Neurosci. 2004 Feb 11;24(6):1406-15. (PMID: 14960613)
Trends Neurosci. 2007 Jun;30(6):268-75. (PMID: 17467065)
Biochem Biophys Res Commun. 2007 Jun 15;357(4):1154-9. (PMID: 17462592)
Nat Methods. 2008 Jan;5(1):49-51. (PMID: 18084299)
Trends Cell Biol. 2004 Jun;14(6):303-11. (PMID: 15183187)
Nat Neurosci. 2013 Apr;16(4):441-8. (PMID: 23455608)
Neuron. 2013 May 8;78(3):510-22. (PMID: 23664616)
Neuron. 2006 Jul 6;51(1):57-69. (PMID: 16815332)
Neuron. 2001 Nov 8;32(3):415-24. (PMID: 11709153)
J Neurosci. 2006 Oct 4;26(40):10199-208. (PMID: 17021175)
J Cell Biol. 2001 Jan 8;152(1):1-13. (PMID: 11149916)
Traffic. 2008 Jul;9(7):1050-9. (PMID: 18435820)
Neuron. 2004 Feb 19;41(4):521-34. (PMID: 14980202)
Mol Biol Cell. 2013 Jun;24(11):1749-64, S1-5. (PMID: 23596322)
Learn Mem. 2013 Sep 16;20(10):518-30. (PMID: 24042848)
Cold Spring Harb Perspect Biol. 2012 Feb 01;4(2):. (PMID: 22129599)
Development. 1993 Jun;118(2):401-15. (PMID: 8223268)
J Biol Chem. 2003 Feb 21;278(8):5947-51. (PMID: 12511557)
J Cell Biol. 2013 Apr 15;201(2):293-308. (PMID: 23569215)
Cell. 2004 Oct 15;119(2):245-56. (PMID: 15479641)
J Biochem. 2011 Aug;150(2):133-41. (PMID: 21697237)
Neuron. 2000 May;26(2):313-29. (PMID: 10839352)
Neuroscience. 2013 Oct 22;251:120-8. (PMID: 22522472)
Front Mol Neurosci. 2014 Feb 03;7:1. (PMID: 24574959)
Annu Rev Neurosci. 1996;19:545-75. (PMID: 8833454)
Cell Cycle. 2011 Jul 15;10(14):2305-16. (PMID: 21670596)
BMC Dev Biol. 2010 Apr 20;10:40. (PMID: 20406475)
EMBO J. 2009 Dec 16;28(24):3879-92. (PMID: 19875983)
J Neurosci. 2011 Jun 15;31(24):8862-9. (PMID: 21677170)
Trends Biochem Sci. 2009 Dec;34(12):620-7. (PMID: 19875293)

0 (Cell Cycle Proteins)
0 (Drosophila Proteins)
0 (HIW protein, Drosophila)
0 (Multiprotein Complexes)
0 (Nerve Tissue Proteins)
0 (TSC1 protein, Drosophila)
0 (WASp protein, Drosophila)
0 (Wiskott-Aldrich Syndrome Protein)
0 (gig protein, Drosophila)
EC 2.7.1.- (trc protein, Drosophila)
EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)

Date Created: 20150923 Date Completed: 20160531 Latest Revision: 20240327

20240327

PMC4578898

10.1371/journal.pone.0138188

26393506