Neurexin, Neuroligin and Wishful Thinking coordinate synaptic cytoarchitecture and growth at neuromuscular junctions

Swati Banerjee, Anandakrishnan Venkatesan, Manzoor Bhat

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Trans-synaptic interactions involving Neurexins and Neuroligins are thought to promote adhesive interactions for precise alignment of the pre- and postsynaptic compartments and organize synaptic macromolecular complexes across species. In Drosophila, while Neurexin (Dnrx) and Neuroligins (Dnlg) are emerging as central organizing molecules at synapses, very little is known of the spectrum of proteins that might be recruited to the Dnrx/Dnlg trans-synaptic interface for organization and growth of the synapses. Using full length and truncated forms of Dnrx and Dnlg1 together with cell biological analyses and genetic interactions, we report novel functions of Dnrx and Dnlg1 in clustering of pre- and postsynaptic proteins, coordination of synaptic growth and ultrastructural organization. We show that Dnrx and Dnlg1 extracellular and intracellular regions are required for proper synaptic growth and localization of Dnlg1 and Dnrx, respectively. dnrx and dnlg1 single and double mutants display altered subcellular distribution of Discs large (Dlg), which is the homolog of mammalian post-synaptic density protein, PSD95. dnrx and dnlg1 mutants also display ultrastructural defects ranging from abnormal active zones, misformed pre- and post-synaptic areas with underdeveloped subsynaptic reticulum. Interestingly, dnrx and dnlg1 mutants have reduced levels of the Bone Morphogenetic Protein (BMP) receptor Wishful thinking (Wit), and Dnrx and Dnlg1 are required for proper localization and stability of Wit. In addition, the synaptic overgrowth phenotype resulting from the overexpression of Dnrx fails to manifest in wit mutants. Phenotypic analyses of dnrx/wit and dnlg1/wit mutants indicate that Dnrx/Dnlg1/Wit coordinate synaptic growth and architecture at the NMJ. Our findings also demonstrate that loss of Dnrx and Dnlg1 leads to decreased levels of the BMP co-receptor, Thickveins and the downstream effector phosphorylated Mad at the Neuromuscular Junction (NMJ) synapses indicating that Dnrx/Dnlg1 regulate components of the BMP signaling pathway. Together our findings reveal that Dnrx/Dnlg are at the core of a highly orchestrated process that combines adhesive and signaling mechanisms to ensure proper synaptic organization and growth during NMJ development.

Original languageEnglish (US)
Pages (from-to)9-24
Number of pages16
JournalMolecular and Cellular Neuroscience
Volume78
DOIs
StatePublished - Jan 1 2017

Fingerprint

Neuromuscular Junction
Drosophila
Growth
Wit and Humor
Bone Morphogenetic Protein Receptors
Synapses
Adhesives
Macromolecular Substances
Post-Synaptic Density
Reticulum
Bone Morphogenetic Proteins
Proteins
Cluster Analysis

Keywords

  • Neurexin
  • Neuroligin 1
  • Neuromuscular junctions
  • Subsynaptic reticulum
  • Synaptic growth
  • Wishful Thinking

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Neurexin, Neuroligin and Wishful Thinking coordinate synaptic cytoarchitecture and growth at neuromuscular junctions. / Banerjee, Swati; Venkatesan, Anandakrishnan; Bhat, Manzoor.

In: Molecular and Cellular Neuroscience, Vol. 78, 01.01.2017, p. 9-24.

Research output: Contribution to journalArticle

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