Osmotic stress activates RIPK3/MLKL-mediated necroptosis by increasing cytosolic pH through a plasma membrane Na < sup > + < /sup > /H < sup > + < /sup > exchanger
We report here that necroptosis is also activated by extracellular osmotic stresses. Unlike the previously identified inducers of necroptosis, osmotic stress stimulated necroptosis through the direct activation of the kinase activity of RIPK3 by an increase in cytosolic pH mediated by the Na+/H+ exchanger SLC9A1. Knockout, knockdown, or chemical inhibition of SLC9A1 blocked necroptosis induced by osmotic stresses. Moreover, setting intracellular pH at above-physiological values directly activated RIPK3 and necroptosis. The activation of RIPK3 by osmotic stresses did not require its RHIM domain, the protein-interacting doma...
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Wenbin Zhang Weiliang Fan Jia Guo Xiaodong Wang Source Type: research

The cell polarity protein Vangl2 in the muscle shapes the neuromuscular synapse by binding to and regulating the tyrosine kinase MuSK
Sci Signal. 2022 May 17;15(734):eabg4982. doi: 10.1126/scisignal.abg4982. Epub 2022 May 17.ABSTRACTThe development of the neuromuscular junction (NMJ) requires dynamic trans-synaptic coordination orchestrated by secreted factors, including Wnt family morphogens. To investigate how these synaptic cues in NMJ development are transduced, particularly in the regulation of acetylcholine receptor (AChR) accumulation in the postsynaptic membrane, we explored the function of Van Gogh-like protein 2 (Vangl2), a core component of Wnt planar cell polarity signaling. We found that conditional, muscle-specific ablation of Vangl2 in mic...
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Myriam Bo ëx Steve Cottin Marius Halliez St éphanie Bauché C éline Buon Nathalie Sans Mireille Montcouquiol Jordi Molg ó Muriel Amar Arnaud Ferry M égane Lemaitre Andr ée Rouche Dominique Langui Asha Baskaran Bertrand Fontaine Julien Mess éant Lau Source Type: research

Lymph node colonization and metastasis
Sci Signal. 2022 May 17;15(734):eadc9985. doi: 10.1126/scisignal.adc9985. Epub 2022 May 17.ABSTRACTLymph nodes open an immune-tolerant pathway for metastasis.PMID:35580170 | DOI:10.1126/scisignal.adc9985 (Source: Science Signaling)
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Amy E Baek Source Type: research

Osmotic stress activates RIPK3/MLKL-mediated necroptosis by increasing cytosolic pH through a plasma membrane Na < sup > + < /sup > /H < sup > + < /sup > exchanger
We report here that necroptosis is also activated by extracellular osmotic stresses. Unlike the previously identified inducers of necroptosis, osmotic stress stimulated necroptosis through the direct activation of the kinase activity of RIPK3 by an increase in cytosolic pH mediated by the Na+/H+ exchanger SLC9A1. Knockout, knockdown, or chemical inhibition of SLC9A1 blocked necroptosis induced by osmotic stresses. Moreover, setting intracellular pH at above-physiological values directly activated RIPK3 and necroptosis. The activation of RIPK3 by osmotic stresses did not require its RHIM domain, the protein-interacting doma...
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Wenbin Zhang Weiliang Fan Jia Guo Xiaodong Wang Source Type: research

The cell polarity protein Vangl2 in the muscle shapes the neuromuscular synapse by binding to and regulating the tyrosine kinase MuSK
Sci Signal. 2022 May 17;15(734):eabg4982. doi: 10.1126/scisignal.abg4982. Epub 2022 May 17.ABSTRACTThe development of the neuromuscular junction (NMJ) requires dynamic trans-synaptic coordination orchestrated by secreted factors, including Wnt family morphogens. To investigate how these synaptic cues in NMJ development are transduced, particularly in the regulation of acetylcholine receptor (AChR) accumulation in the postsynaptic membrane, we explored the function of Van Gogh-like protein 2 (Vangl2), a core component of Wnt planar cell polarity signaling. We found that conditional, muscle-specific ablation of Vangl2 in mic...
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Myriam Bo ëx Steve Cottin Marius Halliez St éphanie Bauché C éline Buon Nathalie Sans Mireille Montcouquiol Jordi Molg ó Muriel Amar Arnaud Ferry M égane Lemaitre Andr ée Rouche Dominique Langui Asha Baskaran Bertrand Fontaine Julien Mess éant Lau Source Type: research

Lymph node colonization and metastasis
Sci Signal. 2022 May 17;15(734):eadc9985. doi: 10.1126/scisignal.adc9985. Epub 2022 May 17.ABSTRACTLymph nodes open an immune-tolerant pathway for metastasis.PMID:35580170 | DOI:10.1126/scisignal.adc9985 (Source: Science Signaling)
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Amy E Baek Source Type: research

Osmotic stress activates RIPK3/MLKL-mediated necroptosis by increasing cytosolic pH through a plasma membrane Na < sup > + < /sup > /H < sup > + < /sup > exchanger
We report here that necroptosis is also activated by extracellular osmotic stresses. Unlike the previously identified inducers of necroptosis, osmotic stress stimulated necroptosis through the direct activation of the kinase activity of RIPK3 by an increase in cytosolic pH mediated by the Na+/H+ exchanger SLC9A1. Knockout, knockdown, or chemical inhibition of SLC9A1 blocked necroptosis induced by osmotic stresses. Moreover, setting intracellular pH at above-physiological values directly activated RIPK3 and necroptosis. The activation of RIPK3 by osmotic stresses did not require its RHIM domain, the protein-interacting doma...
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Wenbin Zhang Weiliang Fan Jia Guo Xiaodong Wang Source Type: research

The cell polarity protein Vangl2 in the muscle shapes the neuromuscular synapse by binding to and regulating the tyrosine kinase MuSK
Sci Signal. 2022 May 17;15(734):eabg4982. doi: 10.1126/scisignal.abg4982. Epub 2022 May 17.ABSTRACTThe development of the neuromuscular junction (NMJ) requires dynamic trans-synaptic coordination orchestrated by secreted factors, including Wnt family morphogens. To investigate how these synaptic cues in NMJ development are transduced, particularly in the regulation of acetylcholine receptor (AChR) accumulation in the postsynaptic membrane, we explored the function of Van Gogh-like protein 2 (Vangl2), a core component of Wnt planar cell polarity signaling. We found that conditional, muscle-specific ablation of Vangl2 in mic...
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Myriam Bo ëx Steve Cottin Marius Halliez St éphanie Bauché C éline Buon Nathalie Sans Mireille Montcouquiol Jordi Molg ó Muriel Amar Arnaud Ferry M égane Lemaitre Andr ée Rouche Dominique Langui Asha Baskaran Bertrand Fontaine Julien Mess éant Lau Source Type: research

Lymph node colonization and metastasis
Sci Signal. 2022 May 17;15(734):eadc9985. doi: 10.1126/scisignal.adc9985. Epub 2022 May 17.ABSTRACTLymph nodes open an immune-tolerant pathway for metastasis.PMID:35580170 | DOI:10.1126/scisignal.adc9985 (Source: Science Signaling)
Source: Science Signaling - May 17, 2022 Category: Biomedical Science Authors: Amy E Baek Source Type: research

ASB4 modulates central melanocortinergic neurons and calcitonin signaling to control satiety and glucose homeostasis
Sci Signal. 2022 May 10;15(733):eabj8204. doi: 10.1126/scisignal.abj8204. Epub 2022 May 10.ABSTRACTVariants in the gene encoding ankyrin repeat and SOCS box-containing 4 (ASB4) are linked to human obesity. Here, we characterized the pathways underlying the metabolic functions of ASB4. Hypothalamic Asb4 expression was suppressed by fasting in wild-type mice but not in mice deficient in AgRP, which encodes Agouti-related protein (AgRP), an appetite-stimulating hormone, suggesting that ASB4 is a negative target of AgRP. Many ASB4 neurons in the brain were adjacent to AgRP terminals, and feeding induced by AgRP neuronal activa...
Source: Science Signaling - May 10, 2022 Category: Biomedical Science Authors: Eirini Vagena Jasmina Crneta Pauline Engstr öm Li He Ernie Yulyaningsih Nikita L Korpel Rachel T Cheang Tomas P Bachor Alyssa Huang Guillermina Michel Kush Attal David I Berrios Martin Valdearcos Suneil K Koliwad David P Olson Chun-Xia Yi Allison W Xu Source Type: research

Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling
Sci Signal. 2022 May 10;15(733):eabh3066. doi: 10.1126/scisignal.abh3066. Epub 2022 May 10.ABSTRACTSynapses connect discrete neurons into vast networks that send, receive, and encode diverse forms of information. Synaptic function and plasticity, the neuronal process of adapting to diverse and variable inputs, depend on the dynamic nature of synaptic molecular components, which is mediated in part by cell adhesion signaling pathways. Here, we found that the enzyme biliverdin reductase (BVR) physically links together key focal adhesion signaling molecules at the synapse. BVR-null (BVR-/-) mice exhibited substantial deficits...
Source: Science Signaling - May 10, 2022 Category: Biomedical Science Authors: Chirag Vasavda Evan R Semenza Jason Liew Ruchita Kothari Ryan S Dhindsa Shruthi Shanmukha Anthony Lin Robert Tokhunts Cristina Ricco Adele M Snowman Lauren Albacarys Francesco Pastore Cristian Ripoli Claudio Grassi Eugenio Barone Michael D Kornberg Xinzho Source Type: research

Cleaved to keep dying cells alive
Sci Signal. 2022 May 10;15(733):eabq8516. doi: 10.1126/scisignal.abq8516. Epub 2022 May 10.ABSTRACTUpon DNA damage, caspase-3 sends the kinase AMPK to the nucleus to prevent apoptotic progression.PMID:35536886 | DOI:10.1126/scisignal.abq8516 (Source: Science Signaling)
Source: Science Signaling - May 10, 2022 Category: Biomedical Science Authors: Leslie K Ferrarelli Source Type: research

ASB4 modulates central melanocortinergic neurons and calcitonin signaling to control satiety and glucose homeostasis
Sci Signal. 2022 May 10;15(733):eabj8204. doi: 10.1126/scisignal.abj8204. Epub 2022 May 10.ABSTRACTVariants in the gene encoding ankyrin repeat and SOCS box-containing 4 (ASB4) are linked to human obesity. Here, we characterized the pathways underlying the metabolic functions of ASB4. Hypothalamic Asb4 expression was suppressed by fasting in wild-type mice but not in mice deficient in AgRP, which encodes Agouti-related protein (AgRP), an appetite-stimulating hormone, suggesting that ASB4 is a negative target of AgRP. Many ASB4 neurons in the brain were adjacent to AgRP terminals, and feeding induced by AgRP neuronal activa...
Source: Science Signaling - May 10, 2022 Category: Biomedical Science Authors: Eirini Vagena Jasmina Crneta Pauline Engstr öm Li He Ernie Yulyaningsih Nikita L Korpel Rachel T Cheang Tomas P Bachor Alyssa Huang Guillermina Michel Kush Attal David I Berrios Martin Valdearcos Suneil K Koliwad David P Olson Chun-Xia Yi Allison W Xu Source Type: research

Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling
Sci Signal. 2022 May 10;15(733):eabh3066. doi: 10.1126/scisignal.abh3066. Epub 2022 May 10.ABSTRACTSynapses connect discrete neurons into vast networks that send, receive, and encode diverse forms of information. Synaptic function and plasticity, the neuronal process of adapting to diverse and variable inputs, depend on the dynamic nature of synaptic molecular components, which is mediated in part by cell adhesion signaling pathways. Here, we found that the enzyme biliverdin reductase (BVR) physically links together key focal adhesion signaling molecules at the synapse. BVR-null (BVR-/-) mice exhibited substantial deficits...
Source: Science Signaling - May 10, 2022 Category: Biomedical Science Authors: Chirag Vasavda Evan R Semenza Jason Liew Ruchita Kothari Ryan S Dhindsa Shruthi Shanmukha Anthony Lin Robert Tokhunts Cristina Ricco Adele M Snowman Lauren Albacarys Francesco Pastore Cristian Ripoli Claudio Grassi Eugenio Barone Michael D Kornberg Xinzho Source Type: research

Cleaved to keep dying cells alive
Sci Signal. 2022 May 10;15(733):eabq8516. doi: 10.1126/scisignal.abq8516. Epub 2022 May 10.ABSTRACTUpon DNA damage, caspase-3 sends the kinase AMPK to the nucleus to prevent apoptotic progression.PMID:35536886 | DOI:10.1126/scisignal.abq8516 (Source: Science Signaling)
Source: Science Signaling - May 10, 2022 Category: Biomedical Science Authors: Leslie K Ferrarelli Source Type: research