AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis

Cai, Xiaoyu; Li, Hongjie; Safyan, Abu; Gawlik, Jennifer; Pyrowolakis, George; Jasper, Heinrich

doi:10.1038/s41467-019-10926-2

Cited by 23 publications

(23 citation statements)

References 64 publications

(105 reference statements)

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“…By contrast, in the Drosophila midgut, hyperactivation of many pro-regeneration factors can cause hyperplasia (Biteau and Jasper, 2011;Johansson et al, 2019), and little is known about the mechanisms that actively turn off the regeneration program. In the regenerating midgut, two distinct modes of BMP/Decapentaplegic (Dpp) signaling differentiate between the pro-and anti-regenerative states (Ayyaz et al, 2015;Tracy Cai et al, 2019). After bacterial challenge, the BMP-family receptor Punt binds to its co-receptor Saxophone and drives pro-regeneration gene expression, mediated by the transcription factor Smad on X (Smox).…”

Section: Turning Regeneration Offmentioning

confidence: 99%

Model systems for regeneration: Drosophila

2020

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Drosophila melanogaster has historically been a workhorse model organism for studying developmental biology. In addition, Drosophila is an excellent model for studying how damaged tissues and organs can regenerate. Recently, new precision approaches that enable both highly targeted injury and genetic manipulation have accelerated progress in this field. Here, we highlight these techniques and review examples of recently discovered mechanisms that regulate regeneration in Drosophila larval and adult tissues. We also discuss how, by applying these powerful approaches, studies of Drosophila can continue to guide the future of regeneration research.

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Section: Turning Regeneration Offmentioning

confidence: 99%

Model systems for regeneration: Drosophila

2020

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“…Surprisingly, this ALK-1 endocytosis was not mediated by Clathrin heavy chain [60]. At the Drosophila NMJ, perturbing endocytosis results in upregulated BMP signaling [11], whereas in Drosophila wing discs and intestinal stem cells, endocytosis facilitates the signaling cascade by internalizing Tkv [61,62], pointing towards a tissue-specific mechanism. Our results suggest a model where bulk membrane endocytosis is insufficient in removing Tkv from the plasma membrane; besides, the synapses in 2-adaptin mutants fail to recycle remaining receptors from early endosomes leading to enhanced signaling and drastic NMJ growth defects.…”

Section: 2-adaptin Regulates Trafficking Of Type I Bmp Receptor Thimentioning

confidence: 95%

AP2 regulates Thickveins trafficking through Rab11 to attenuate NMJ growth signaling inDrosophila

Dwivedi

Choudhury

Patnaik

et al. 2021

Preprint

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Compromised endocytosis in neurons leads to synapse overgrowth and altered organization of synaptic proteins. However, the molecular players and the signaling pathways which regulate the process remains poorly understood. Here we show that σ2-adaptin, one of the subunits of the AP2-complex, genetically interacts with BMP type I receptor, Thickveins (Tkv), and Daughter against decapentaplegic (Dad), two of the components of BMP signaling. We found that mutations in σ2-adaptin lead to an accumulation of Tkv receptors at the NMJ and results in a significant reduction in Tkv-positive early endosomes in the presynaptic terminals. Interestingly, the level of small GTPase Rab11 was significantly reduced in the σ2-adaptin mutant synapses. Consistent with the role of σ2-adaptin and Rab11 in the regulation of the same signaling pathway, a mutation in Rab11 or overexpression of a GDP-locked form of Rab11 (Rab11S25N) phenocopies the morphological and signaling defects of the σ2-adaptin mutants. Finally, we demonstrate that σ2-adaptin mutants show an accumulation of large vesicles and massive membranous structures, akin to endosomes at the synapse. Thus, we propose a model in which AP2 regulates Tkv internalization and recycling through a process that requires Rab11 activity to control the synaptic growth.

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“…Flies containing UAS_NSlmb-vhhGFP4 (deGradFP), tkv [ko,attP] ( tkv [def]) or Tkv3×HA have been previously described ( Caussinus et al, 2011 ; Norman et al, 2016 ; Tracy Cai et al, 2019 ). UASpH2Av::Flag-HA (H2Av-Flag-HA) flies were a kind gift from N. Iovino's group (Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany).…”

Section: Methodsmentioning

confidence: 99%

Protein manipulation using single copies of short peptide tags in cultured cells and in Drosophila melanogaster

et al. 2021

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Cellular development and function rely on highly dynamic molecular interactions among proteins distributed in all cell compartments. Analysis of these interactions has been one of the main topics in cellular and developmental research and has been mostly achieved by the manipulation of proteins of interest (POIs) at the genetic level. Although genetic strategies significantly contributed to our current understanding, targeting specific interactions of POIs in a time- and space-controlled manner or analyzing the role of POIs in dynamic cellular processes such as cell migration or cell division would profit from more direct approaches. The recent development of specific protein binders, which can be expressed and function intracellularly, along with advancement in synthetic biology, have contributed to the creation of a new toolbox for direct protein manipulations. Here, we selected a number of short tag epitopes for which protein binders from different scaffolds have been generated and showed that single copies of these tags allowed efficient POIs binding and manipulation in living cells. Using Drosophila, we also find that single short tags can be utilized for POI manipulation in vivo.

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AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis

Cited by 23 publications

References 64 publications

Model systems for regeneration: Drosophila

Model systems for regeneration: Drosophila

AP2 regulates Thickveins trafficking through Rab11 to attenuate NMJ growth signaling inDrosophila

Protein manipulation using single copies of short peptide tags in cultured cells and in Drosophila melanogaster

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