Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS

McIlroy, Graham; Földi, István; Aurikko, Jukka P.; Wentzell, Jill S.; Lim, Mei Ann; Fenton, J. C.; Hidalgo, Alicia

doi:10.1038/nn.3474

Cited by 100 publications

(174 citation statements)

References 53 publications

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“…Drosophila Toll receptors are highly expressed during embryogenesis, pointing to developmental functions (49,54). Indeed, a subset of Toll receptors, including Toll-7, function as neurotrophin receptors and are activated by members of the Spaetzle family in the developing nervous system (36,55). Drosophila Toll receptors were also recently shown to function as adhesion molecules during elongation of the antero-posterior axis of the embryo (56).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity

Lamiable

Arnold

Faria

et al. 2016

J Virol

112

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Antiviral immunity in the model organism Drosophila melanogaster involves the broadly active intrinsic mechanism of RNA interference (RNAi) and virus-specific inducible responses. Here, using a panel of six viruses, we investigated the role of hemocytes and autophagy in the control of viral infections. Injection of latex beads to saturate phagocytosis, or genetic depletion of hemocytes, resulted in decreased survival and increased viral titers following infection with Cricket paralysis virus (CrPV), Flock House virus (FHV), and vesicular stomatitis virus (VSV) but had no impact on Drosophila C virus (DCV), Sindbis virus (SINV), and Invertebrate iridescent virus 6 (IIV6) infection. In the cases of CrPV and FHV, apoptosis was induced in infected cells, which were phagocytosed by hemocytes. In contrast, VSV did not trigger any significant apoptosis but we confirmed that the autophagy gene Atg7 was required for full virus resistance, suggesting that hemocytes use autophagy to recognize the virus. However, this recognition does not depend on the Toll-7 receptor. Autophagy had no impact on DCV, CrPV, SINV, or IIV6 infection and was required for replication of the sixth virus, FHV. Even in the case of VSV, the increases in titers were modest in Atg7 mutant flies, suggesting that autophagy does not play a major role in antiviral immunity in Drosophila. Altogether, our results indicate that, while autophagy plays a minor role, phagocytosis contributes to virus-specific immune responses in insects. IMPORTANCEPhagocytosis and autophagy are two cellular processes that involve lysosomal degradation and participate in Drosophila immunity. Using a panel of RNA and DNA viruses, we have addressed the contribution of phagocytosis and autophagy in the control of viral infections in this model organism. We show that, while autophagy plays a minor role, phagocytosis contributes to virusspecific immune responses in Drosophila. This work brings to the front a novel facet of antiviral host defense in insects, which may have relevance in the control of virus transmission by vector insects or in the resistance of beneficial insects to viral pathogens.

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Section: Discussionmentioning

confidence: 99%

Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity

Lamiable

Arnold

Faria

et al. 2016

J Virol

112

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“…No orthologs of the vertebrate NT receptors have been found in Drosophila. Interesting, the Tolllike receptor (TLR) proteins Toll-6 and Toll-7 were shown to bind and genetically interact with DNT1 and DNT2, revealing an unexpected neurotrophic function for the Toll family in Drosophila (McIlroy et al 2013).…”

Section: Mechanisms Regulating Growth and Plasticitymentioning

confidence: 99%

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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“…This finding highlights a dual role of TrkC as a neurotrophin receptor and as a trans-synaptic adhesion molecule. Similarly, Drosophila Toll-like receptors utilize their LRR domains to function either as a repulsive cue to locally inhibit the innervation of motor neuron axons into the target tissue or as neurotrophin receptors [48].…”

Section: Lrr Transmembrane Proteins and Nervous System Developmentmentioning

confidence: 99%

Lrig1 is a cell‐intrinsic modulator of hippocampal dendrite complexity and BDNF signaling

et al. 2016

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Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development.

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Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS

Cited by 100 publications

References 53 publications

Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity

Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity

Transmission, Development, and Plasticity of Synapses

Lrig1 is a cell‐intrinsic modulator of hippocampal dendrite complexity and BDNF signaling

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