Tricornered kinase regulates synapse development by regulating the levels of Wiskott-Aldrich syndrome protein

Rajalaxmi Natarajan, Kara Barber, Amanda Buckley, Phillip Cho, Anuoluwapo Egbejimi, Yogesh Wairkar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0138188
JournalPLoS One
Volume10
Issue number9
DOIs
StatePublished - Sep 22 2015

Fingerprint

Wiskott-Aldrich Syndrome Protein
synapse
Synapses
phosphotransferases (kinases)
Phosphotransferases
Sirolimus
Tuberous Sclerosis
proteins
sclerosis
Neuromuscular Junction
Protein-Serine-Threonine Kinases
Neurology
Transcription
mutants
Drosophila
Neurons
Actins
multiprotein complexes
Polymerization
threonine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tricornered kinase regulates synapse development by regulating the levels of Wiskott-Aldrich syndrome protein. / Natarajan, Rajalaxmi; Barber, Kara; Buckley, Amanda; Cho, Phillip; Egbejimi, Anuoluwapo; Wairkar, Yogesh.

In: PLoS One, Vol. 10, No. 9, e0138188, 22.09.2015.

Research output: Contribution to journalArticle

Natarajan, Rajalaxmi ; Barber, Kara ; Buckley, Amanda ; Cho, Phillip ; Egbejimi, Anuoluwapo ; Wairkar, Yogesh. / Tricornered kinase regulates synapse development by regulating the levels of Wiskott-Aldrich syndrome protein. In: PLoS One. 2015 ; Vol. 10, No. 9.
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