scholarly journals Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates

2013 ◽  
Vol 382 (2) ◽  
pp. 538-554 ◽  
Author(s):  
Iryna Kozmikova ◽  
Simona Candiani ◽  
Peter Fabian ◽  
Daniela Gurska ◽  
Zbynek Kozmik
2018 ◽  
Vol 115 (47) ◽  
pp. E11168-E11177 ◽  
Author(s):  
Iksung Jin ◽  
Hiroshi Udo ◽  
Russell Nicholls ◽  
Huixiang Zhu ◽  
Eric R. Kandel ◽  
...  

Whereas short-term plasticity is often initiated on one side of the synapse, long-term plasticity involves coordinated changes on both sides, implying extracellular signaling. We have investigated the possible signaling role of an Aplysia neurotrophin (ApNT) in facilitation induced by serotonin (5HT) at sensory-to-motor neuron synapses in culture. ApNT is an ortholog of mammalian BDNF, which has been reported to act as either an anterograde, retrograde, or autocrine signal, so that its pre- and postsynaptic sources and targets remain unclear. We now report that ApNT acts as a presynaptic autocrine signal that forms part of a positive feedback loop with ApTrk and PKA. That loop stimulates spontaneous transmitter release, which recruits postsynaptic mechanisms, and presynaptic protein synthesis during the transition from short- to intermediate-term facilitation and may also initiate gene regulation to trigger the transition to long-term facilitation. These results suggest that a presynaptic ApNT feedback loop plays several key roles during consolidation of learning-related synaptic plasticity.


2013 ◽  
Vol 9 (1) ◽  
pp. 690 ◽  
Author(s):  
Yassine X Bouchoucha ◽  
Jürgen Reingruber ◽  
Charlotte Labalette ◽  
Michel A Wassef ◽  
Elodie Thierion ◽  
...  

2020 ◽  
Author(s):  
Elliot Dine ◽  
Ellen H. Reed ◽  
Jared E. Toettcher

AbstractProtein clusters and condensates are pervasive in mammalian signaling. Yet how the signaling capacity of higher-order assemblies differs from simpler forms of molecular organization is still poorly understood. Here, we present an optogenetic approach to switch between light-induced clusters and simple protein heterodimers with a single point mutation. We apply this system to study how clustering affects signaling from the kinase Zap70 and its substrate LAT, proteins that normally form membrane-localized clusters during T cell activation. We find that light-induced clusters of LAT and Zap70 trigger potent activation of downstream signaling pathways even in non-T cells, whereas one-to-one dimers do not. We provide evidence that clusters harbor a local positive feedback loop between three components: Zap70, LAT, and Src-family kinases that bind to phosphorylated LAT and further activate Zap70. Overall, our study provides evidence for a specific role of protein condensates in cell signaling, and identifies a simple biochemical circuit that can robustly sense protein oligomerization state.Highlights-A general system for studying the role of protein clusters versus dimers.-Membrane clusters of the kinase Zap70 and its substrate LAT trigger potent downstream signaling.-Clustering Zap70 with LAT is required for full activation of Zap70 kinase activity.-A positive feedback loop connects phosphorylated LAT to Zap70 activation via Src-family kinases.


2012 ◽  
Vol 189 (6) ◽  
pp. 3085-3091 ◽  
Author(s):  
Mizuho Hasegawa ◽  
Nobuhiko Kamada ◽  
Yizu Jiao ◽  
Meng Zhen Liu ◽  
Gabriel Núñez ◽  
...  

2020 ◽  
Vol 61 (3) ◽  
pp. 352-367 ◽  
Author(s):  
Spoorthy Pathikonda ◽  
Shuk Han Cheng ◽  
Kwan Ngok Yu

ABSTRACT Radiation-induced rescue effect (RIRE) in cells refers to the phenomenon where irradiated cells (IRCs) receive help from feedback signals produced by partnered bystander unirradiated cells (UIRCs) or from the conditioned medium (CM) that has previously conditioned the UIRCs. In the present work, we explored the role of poly (ADP-ribose) polymerase 1 (PARP1) regulation in RIRE and the positive feedback loop between PARP1 and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-κB) in RIRE using various cell lines, including HeLa, MCF7, CNE-2 and HCT116 cells. We first found that when the IRCs (irradiated with 2 Gy X-ray) were treated with CM, the relative mRNA expression levels of both tumor suppressor p53-binding protein 1 (53BP1) and PARP1, the co-localization factor between 53BP1 and γH2AX as well as the fluorescent intensity of PARP1 were reduced. We also found that IRCs treated with the PARP1 inhibitor, Olaparib (AZD2281) had a higher 53BP1 expression. These results illustrated that PARP1 was involved in RIRE transcriptionally and translationally. We further revealed that treatment of IRCs with CM together with Olaparib led to significantly lower mRNA expression levels and fluorescent intensities of NF-κB, while treatment of IRCs with CM together the NF-κB inhibitor BAY-11-7082 led to significantly lower mRNA expression levels as well as fluorescent intensities of PARP1. These results illustrated that PARP1 and NF-κB were involved in the positive feedback loop transcriptionally and translationally. Thus, the results supported the occurrence of a PARP1–NF-κB positive feedback loop in RIRE. The present work provided insights into potential exploitation of inhibition of PARP1 and/or the PARP1–NF-κB positive feedback loop in designing adjuncts to cancer radiotherapeutics.


2020 ◽  
Author(s):  
Yiwen Xia ◽  
Jialun Lv ◽  
Tianlu Jiang ◽  
Bowen Li ◽  
Zhongyuan He ◽  
...  

Abstract Background: Circular RNAs (circRNAs) have emerged as a new subclass of regulatory RNAs that exert critical roles in various cancers. Cancer stem cells (CSCs), a small subset of cancer cells, are believed to possess the capacities to initiate tumorigenesis and promote progression. Although accumulating evidences have suggested that cells with CSC-like properties are crucial for the malignance process of gastric cancer (GC), it remains inexplicit whether circRNAs are interrelated with the acquisition of CSC-like properties in GC.Methods: circFAM73A expression was analyzed by GEO datasets and verified in GC samples. The role of circFAM73A on GC cell proliferation, migration, cisplatin resistance and CSC-like properties were determined by a series of functional experiment both in vitro and in vivo. RNA pull down was used to explore the miRNAs and proteins binding to circFAM73A. Bioinformatic analysis and experimental verification confirmed the downstream of circFAM73A. The regulation of HMGA2 on circFAM73A was verified by ChIP and RIP assays.Results: Elevated circFAM73A expression was confirmed in GC tissues and higher circFAM73A predicts poor prognosis of GC patients. The upregulation of circFAM73A enhanced CSC-like properties in GC, thus, exerting the facilitating role on cell proliferation, migration and cisplatin resistance. Mechanistically, circFAM73A promoted GC malignancy by regulating miR-490-3p/HMGA2 in a positive feedback loop and recruiting HNRNPK to facilitate β-catenin stabilization. Moreover, HMGA2 further enhanced E2F1 and HNRNPL activity, which in turn promotes circFAM73A expression.Conclusions: Our work demonstrates the crucial role of circFAM73A on GC CSC-like properties and uncovers a positive feedback loop on circFAM73A regulation that leads to the progression of gastric cancer, which may provide a new insight for circRNA-based diagnostic and therapeutic strategies.


2009 ◽  
Vol 21 (4) ◽  
pp. 1080-1094 ◽  
Author(s):  
Yeon Hee Kang ◽  
Victor Kirik ◽  
Martin Hulskamp ◽  
Kyoung Hee Nam ◽  
Katherine Hagely ◽  
...  

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