Nidogens are therapeutic targets for the prevention of tetanus

Bercsényi, Kinga; Schmieg, Nathalie; Bryson, J. Barney; Wallace, Martin; Caccin, Paola; Golding, Matthew; Zanotti, Giuseppe; Greensmith, Linda; Nischt, Roswitha; Schiavo, Giampietro

doi:10.1126/science.1258138

Cited by 72 publications

(83 citation statements)

References 43 publications

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“…Since FGRF3 may undergo receptor-mediated endocytosis followed by long-range transport upon stimulation with its ligand, it might be able to mediate the uptake, sorting, and transport of BoNT/A along its trafficking route. Alternatively, BoNT/A could bind extracellular matrix (ECM) components at the NMJ as recently reported for TeNT [118], leading to its sorting to axonal signaling endosomes and transcytosis.…”

Section: Bont Receptorsmentioning

confidence: 95%

See 1 more Smart Citation

Uptake and transport of clostridial neurotoxins

Schmieg

Bercsényi

Schiavo

2015

The Comprehensive Sourcebook of Bacterial Protein Toxins

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Section: Bont Receptorsmentioning

confidence: 95%

“…We recently showed that TeNT interacts with specific ECM components at the NMJ to stimulate uptake of TrkB and formation of signaling endosomes [118]. In particular, the H C domain of TeNT (H C T) directly binds to both nidogen-1 and -2 and selectively targets NMJs containing high levels of nidogen-2.…”

Section: Tent Receptorsmentioning

confidence: 99%

Uptake and transport of clostridial neurotoxins

Schmieg

Bercsényi

Schiavo

2015

The Comprehensive Sourcebook of Bacterial Protein Toxins

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“…Whereas Rab5 is essential for an early step in TeNT sorting, Rab7 plays an essential role in long-range axonal retrograde transport. Endocytosis of TeNT was also recently shown to require the extracellular matrix proteins, Nidogens, at the neuronal surface (37). The endocytosed TeNT-Nidogen complex is retrogradely transported into the cell body to elicit its toxic effects.…”

Section: Figmentioning

confidence: 99%

“…The endocytosed TeNT-Nidogen complex is retrogradely transported into the cell body to elicit its toxic effects. Inhibition of the TeNTNidogen interaction with small Nidogen-derived peptides or genetic ablation of Nidogens prevented the binding of TeNT to neurons and protected mice from TeNT-induced spastic paralysis (37).…”

Section: Figmentioning

confidence: 99%

Signaling Over Distances

Saito

Cavalli

2016

Molecular & Cellular Proteomics

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Neurons are extremely polarized cells. Axon lengths often exceed the dimension of the neuronal cell body by several orders of magnitude. These extreme axonal lengths imply that neurons have mastered efficient mechanisms for long distance signaling between soma and synaptic terminal. These elaborate mechanisms are required for neuronal development and maintenance of the nervous system. Neurons can fine-tune long distance signaling through calcium wave propagation and bidirectional transport of proteins, vesicles, and mRNAs along microtubules. The signal transmission over extreme lengths also ensures that information about axon injury is communicated to the soma and allows for repair mechanisms to be engaged. This review focuses on the different mechanisms employed by neurons to signal over long axonal distances and how signals are interpreted in the soma, with an emphasis on proteomic studies. We also discuss how proteomic approaches could help further deciphering the signaling mechanisms operating over long distance in axons. Neurons have unique and highly polarized morphologies. The axon allows intracellular communication between the cell soma and the distantly located synaptic terminal. The extreme length of axons relative to the cell soma diameter poses great challenges for neuronal development, maintenance, and repair. Anterograde and retrograde axonal transport of proteins vesicles and RNA along the microtubule tracks in the axon is crucial to sustain the required signaling events underlying development and maintenance of the nervous system. The retrograde transport system is also used following axon injury to communicate information from the site of injury back to the soma. Communication between distant axon locations and the cell soma is also ensured by a more rapid signal encoded in calcium waves. Incoming signals from distant axon locations are interpreted by the soma to regulate gene expression for survival or repair. The neuronal epigenome is also influenced by incoming signals to appropriately coordinate transcriptional responses. In this review, we discuss the state of the field regarding the different mechanisms employed by neurons to signal intracellularly over long distances in axons and how signals are interpreted in the cell soma, with an emphasis on proteomic studies. We also discuss how the use of proteomics could further help in understanding long distance signaling system in axons. The communication employed by neurons to signal along dendrites has been reviewed in detail elsewhere (1) and will not be discussed here.Calcium Influx, Back Propagation, and Long Distance Effects-Alterations in axonal calcium levels affect multiple and diverse signaling events, including local protein synthesis and degradation. These local signals can have long distance effects. Axon injury provides a powerful system to study the role of calcium in axonal signaling, because injury-induced calcium influx in the axon triggers important downstream events at the injury site and the soma (Fig.

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“…Recent studies have indicated that CHIKV enters cells in vitro rapidly through clathrin-mediated endocytosis [65]. Our approach which is dependent on fusion to target cells and avoids the side effects of infection could be utilised to further isolate and elucidate the CHIKV entry receptor [66].…”

mentioning

confidence: 99%

Selective transduction of astrocytic and neuronal CNS subpopulations by lentiviral vectors pseudotyped with Chikungunya virus envelope

et al. 2017

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NHAs was observed. In vivo stereotaxic delivery in striatum, thalamus and hippocampus respectively in the adult rat brain revealed localised transduction restricted to striatal astrocytes and hippocampal dentate granule neurons. Transduction of different subtypes of granule neurons from precursor to post-mitotic stages of differentiation was evident in the sub-granular zone and dentate granule cell layer. No significant inflammatory response was observed, but comparable to that of VSV-G pseudotyped lentiviral vectors. Robust longterm expression followed for three months post-transduction along with absence of neuroinflammation, coupled to the selective and unique neuron/glial tropism indicates that these vectors could be useful for modelling and gene therapy studies in the CNS.

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Nidogens are therapeutic targets for the prevention of tetanus

Cited by 72 publications

References 43 publications

Uptake and transport of clostridial neurotoxins

Uptake and transport of clostridial neurotoxins

Signaling Over Distances

Selective transduction of astrocytic and neuronal CNS subpopulations by lentiviral vectors pseudotyped with Chikungunya virus envelope

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