Secreted type of amyloid precursor protein induces glial differentiation by stimulating the BMP/Smad signaling pathway

Kwak, Young-Don; Hendrix, Brandon J.; Sugaya, Kimio

doi:10.1016/j.bbrc.2014.03.139

Cited by 24 publications

(19 citation statements)

References 36 publications

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“…Whereas most have been used for research applications, some have been shown to have neutralization activities. For instance, clone 3H2, a mouse monoclonal antibody, was able to inhibit BMP4-mediated glial differentiation, 27 while anti-BMP4 clone 66119 was shown to inhibit BMP4-mediated smooth muscle cell proliferation. 28 Surprisingly, the concentrations at which those antibodies were used in those and in other publications 29-31 ranged between 1-10 μg/ml, in contrast to the nanomolar range of which the VHH were shown to be biologically active.…”

Section: Resultsmentioning

confidence: 99%

“…Conventional anti-BMP4 antibodies have been previously reported and used both in research as well as in neutralization experiments. 27,28 Their epitopes, however, have never been tested or disclosed, and their inhibitory capabilities were never compared. In this study, we aimed to decipher their binding epitopes and determine how these correlate with functionality.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas most are only used in research applications, such as Western blot or immunostaining, a few of them have been used for neutralization experiments with limited success due to their low efficacy. 27-31 Llama-derived antibodies or VHH are small (∼15 kDa) fully functional antibodies that lack light chains. Due to their distinct structure, these stable antibodies can bind specifically and with great affinity to their antigens better than the conventional antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of newly developed anti-bone morphogenetic protein 4 llama-derived antibodies with commercially available BMP4 inhibitors

Calpe

Correia

Sancho-Serra

et al. 2016

mAbs

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Due to improved understanding of the role of bone morphogenetic protein 4 (BMP4) in an increasing number of diseases, the development of selective inhibitors of BMP4 is an attractive therapeutic option. The currently available BMP4 inhibitors are not suitable as therapeutics because of their low specificity and low effectiveness. Here, we compared newly generated anti-BMP4 llama-derived antibodies (VHHs) with 3 different types of commercially available BMP4 inhibitors, natural antagonists, small molecule BMPR inhibitors and conventional anti-BMP4 monoclonal antibodies. We found that the anti-BMP4 VHHs were as effective as the natural antagonist or small molecule inhibitors, but had higher specificity. We also showed that commercial anti-BMP4 antibodies were inferior in terms of both specificity and effectiveness. These findings might result from the fact that the VHHs C4C4 and C8C8 target a small region within the BMPR1 epitope of BMP4, whereas the commercial antibodies target other areas of the BMP4 molecule. Our results show that the newly developed anti-BMP4 VHHs are promising antibodies with better specificity and effectivity for inhibition of BMP4, making them an attractive tool for research and for therapeutic applications.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of newly developed anti-bone morphogenetic protein 4 llama-derived antibodies with commercially available BMP4 inhibitors

Calpe

Correia

Sancho-Serra

et al. 2016

mAbs

View full text Add to dashboard Cite

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“…These reports have suggested that there may be causes other than RNA degradation. Indeed, when an extracellular protein enters a cell, complex processes occur for it to exert its function, and signal transduction or defense reactions are often involved (Sawamoto et al, 1996;Wan et al, 2010;Kwak et al, 2014). Thus, S-RNase may trigger signaling pathways or defense responses after its entry into the pollen.…”

Section: Introductionmentioning

confidence: 99%

Apple S‐RNase triggers inhibition of tRNA aminoacylation by interacting with a soluble inorganic pyrophosphatase in growing self‐pollen tubes in vitro

Meng

et al. 2018

New Phytologist

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Apple exhibits S-RNase-based self-incompatibility (SI), in which S-RNase plays a central role in rejecting self-pollen. It has been proposed that the arrest of pollen growth in SI of Solanaceae plants is a consequence of the degradation of pollen rRNA by S-RNase; however, the underlying mechanism in Rosaceae is still unclear. Here, we used S -RNase as a bait to screen an apple pollen cDNA library and characterized an apple soluble inorganic pyrophosphatase (MdPPa) that physically interacted with S-RNases. When treated with self S-RNases, apple pollen tubes showed a marked growth inhibition, as well as a decrease in endogenous soluble pyrophosphatase activity and elevated levels of inorganic pyrophosphate (PPi). In addition, S-RNase was found to bind to two variable regions of MdPPa, resulting in a noncompetitive inhibition of its activity. Silencing of MdPPa expression led to a reduction in pollen tube growth. Interestingly, tRNA aminoacylation was inhibited in self S-RNase-treated or MdPPa-silenced pollen tubes, resulting in the accumulation of uncharged tRNA. Furthermore, we provide evidence showing that this disturbance of tRNA aminoacylation is independent of RNase activity. We propose an alternative mechanism differing from RNA degradation to explain the cytotoxicity of the S-RNase apple SI process.

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“…Recent studies in Rosaceae mainly focus on the downstream signalling cascade likely occurs in SI in order to terminate incompatible pollen tubes growth, such as changes of calcium concentration, actin cytoskeleton depolymerization, burst out of reactive oxygen and tRNA aminoacylation in pollen tubes (Di et al ., ; Li et al ., ; Wang and Zhang, ; Wang et al ., ). Indeed, in general, when an extracellular protein enters a cell, a series of processes will be triggered, including defence response and signal transduction (Kwak et al ., ; Sawamoto et al ., ; Wan et al ., ). In response to undesirable invading substances, plants could activate a wide range of defences which can reduce potential cellular damage (Erb et al ., ; Schuman and Baldwin, ; Wu et al ., ).…”

Section: Introductionmentioning

confidence: 97%

A gamma‐thionin protein from apple, MdD1, is required for defence against S‐RNase‐induced inhibition of pollen tube prior to self/non‐self recognition

Doughty

et al. 2019

Plant Biotechnology Journal

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Summary Apple exhibits S‐RNase‐mediated self‐incompatibility. Although the cytotoxic effect of S‐RNase inside the self‐pollen tube has been studied extensively, the underlying defence mechanism in pollen tube in Rosaceae remains unclear. On exposure to stylar S‐RNase, plant defence responses are activated in the pollen tube; however, how these are regulated is currently poorly understood. Here, we show that entry of both self and non‐self S‐RNase into pollen tubes of apple (Malus domestica) stimulates jasmonic acid (JA) production, in turn inducing the accumulation of MdMYC2 transcripts, a transcription factor in the JA signalling pathway widely considered to be involved in plant defence processes. MdMYC2 acts as a positive regulator in the pollen tube activating expression of MdD1, a gene encoding a defence protein. Importantly, MdD1 was shown to bind to the RNase activity sites of S‐RNase leading to inhibition of enzymatic activity. This work provides intriguing insights into an ancient defence mechanism present in apple pollen tubes where MdD1 likely acts as a primary line of defence to inhibit S‐RNase cytotoxicity prior to self/non‐self recognition.

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Secreted type of amyloid precursor protein induces glial differentiation by stimulating the BMP/Smad signaling pathway

Cited by 24 publications

References 36 publications

Comparison of newly developed anti-bone morphogenetic protein 4 llama-derived antibodies with commercially available BMP4 inhibitors

Comparison of newly developed anti-bone morphogenetic protein 4 llama-derived antibodies with commercially available BMP4 inhibitors

Apple S‐RNase triggers inhibition of tRNA aminoacylation by interacting with a soluble inorganic pyrophosphatase in growing self‐pollen tubes in vitro

A gamma‐thionin protein from apple, MdD1, is required for defence against S‐RNase‐induced inhibition of pollen tube prior to self/non‐self recognition

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