Drosophila Neuroligin3 Regulates Neuromuscular Junction Development and Synaptic Differentiation

Xing, Guanglin; Gan, Guangming; Chen, Dandan; Sun, Mingkuan; Yi, Jukang; Lv, Huihui; Han, Junhai; Xie, Wei

doi:10.1074/jbc.m114.574897

Cited by 45 publications

(76 citation statements)

References 51 publications

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“…In addition, mutants for nrx-1, nlg-1, and nlg-2 each exhibit a dramatic decrease in the number of boutons at the NMJ (Li et al 2007;Banovic et al 2010;Sun et al 2011;Chen et al 2012). In contrast, loss of nlg-3 results in bouton overgrowth (Xing et al 2014). Loss of nlg-1 or nlg-2 has also been noted to produce irregularly shaped or large boutons (Chen et al 2012).…”

Section: Mechanisms Regulating Growth and Plasticitymentioning

confidence: 99%

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Transmission, Development, and Plasticity of Synapses

Harris¹,

2015

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Chemical synapses are sites of contact and information transfer between a neuron and its partner cell. Each synapse is a specialized junction, where the presynaptic cell assembles machinery for the release of neurotransmitter, and the postsynaptic cell assembles components to receive and integrate this signal. Synapses also exhibit plasticity, during which synaptic function and/or structure are modified in response to activity. With a robust panel of genetic, imaging, and electrophysiology approaches, and strong evolutionary conservation of molecular components, Drosophila has emerged as an essential model system for investigating the mechanisms underlying synaptic assembly, function, and plasticity. We will discuss techniques for studying synapses in Drosophila, with a focus on the larval neuromuscular junction (NMJ), a well-established model glutamatergic synapse. Vesicle fusion, which underlies synaptic release of neurotransmitters, has been well characterized at this synapse. In addition, studies of synaptic assembly and organization of active zones and postsynaptic densities have revealed pathways that coordinate those events across the synaptic cleft. We will also review modes of synaptic growth and plasticity at the fly NMJ, and discuss how pre-and postsynaptic cells communicate to regulate plasticity in response to activity. KEYWORDS FlyBook; Drosophila; synapse; neurotransmitter release; synaptic plasticity; active zone; synaptic vesicle TABLE OF CONTENTS Abstract 345Introduction 345

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Section: Mechanisms Regulating Growth and Plasticitymentioning

confidence: 99%

“…Other Nlgs also regulate GluR subunit composition. Nlg-3 promotes A-type clustering (Xing et al 2014). Nlg-2 regulates total GluR abundance and may also affect subunit composition (Sun et al 2011;Chen et al 2012).…”

Section: Ionotropic Glutamate Receptors At the Nmjmentioning

confidence: 99%

Transmission, Development, and Plasticity of Synapses

Harris¹,

2015

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“…Another change in the fly NMJ synapse compared to the pSJ is the appearance of a family of non-catalytic cholinesterase-like molecules, the neuroligins, that are distinct from gliotactin, a non-catalytic cholinesterase-like molecule found at the tricellular pSJ (Genova and Fehon, 2003;Schulte et al, 2003). The neuroligins are important components of synapses and form transynaptic connections with neurexin (Banovic et al, 2010;Chen et al, 2012;Sun et al, 2011;Xing et al, 2014). In contrast, at the pSJ, there is no indication that Nrx-IV binds to gliotactin.…”

Section: The Septate Junction and Its Originsmentioning

confidence: 99%

“…Similarly, rat hippocampal synapses exhibit intermittently occurring complexes in the synaptic cleft (Zuber et al, 2005). However, in Drosophila, when comparing the NMJ synapse to that of the pSJ, a number of changes in the adhesive apparatus are apparent (Banovic et al, 2010;Chen et al, 2012;Koper et al, 2012;Sun et al, 2011;Xing et al, 2014). One important distinction is the presence of neurexin-1 (Nrx-1) and the absence of Nrx-IV.…”

Section: The Septate Junction and Its Originsmentioning

confidence: 99%

Making the connection – shared molecular machinery and evolutionary links underlie the formation and plasticity of occluding junctions and synapses

Harden

Wang

Krieger

2016

Journal of Cell Science

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The pleated septate junction ( pSJ), an ancient structure for cell-cell contact in invertebrate epithelia, has protein components that are found in three more-recent junctional structures, the neuronal synapse, the paranodal region of the myelinated axon and the vertebrate epithelial tight junction. These more-recent structures appear to have evolved through alterations of the ancestral septate junction. During its formation in the developing animal, the pSJ exhibits plasticity, although the final structure is extremely robust. Similar to the immature pSJ, the synapse and tight junctions both exhibit plasticity, and we consider evidence that this plasticity comes at least in part from the interaction of members of the immunoglobulin cell adhesion molecule superfamily with highly regulated membraneassociated guanylate kinases. This plasticity regulation probably arose in order to modulate the ancestral pSJ and is maintained in the derived structures; we suggest that it would be beneficial when studying plasticity of one of these structures to consider the literature on the others. Finally, looking beyond the junctions, we highlight parallels between epithelial and synaptic membranes, which both show a polarized distribution of many of the same proteins -evidence that determinants of apicobasal polarity in epithelia also participate in patterning of the synapse.

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“…These proteins are also implicated in the organization of excitatory glutamatergic and inhibitory GABAergic synapses in mammalian brain (Prange et al 2004; Graf et al 2004; Chih et al 2005; Aoto et al 2015). The functional properties of Nrxs and Nlgs are conserved, as the Drosophila homologs of Neurexin (Dnrx) and Neuroligin (Dnlg) also play critical roles in the assembly and maintenance of the glutamatergic synapses at the larval neuromuscular junctions (NMJ), as lack of either Dnrx or Dnlg shows a significant reduction in synaptic growth at the NMJ (Li et al, 2007; Banovic et al, 2010; Chen et al, 2012; Mozer and Sandstrom, 2012; Xing et al 2014). Despite these studies, many key questions still remain to be addressed in the context of the Drosophila larval NMJ.…”

Section: Introductionmentioning

confidence: 99%

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

Banerjee

Venkatesan

Bhat

2017

Molecular and Cellular Neuroscience

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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 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 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.

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Drosophila Neuroligin3 Regulates Neuromuscular Junction Development and Synaptic Differentiation

Cited by 45 publications

References 51 publications

Transmission, Development, and Plasticity of Synapses

Transmission, Development, and Plasticity of Synapses

Making the connection – shared molecular machinery and evolutionary links underlie the formation and plasticity of occluding junctions and synapses

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

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