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An intestinal zinc sensor regulates food intake and developmental growth 期刊论文
NATURE, 2020, 580 (7802) : 263-+
作者:  Wu, Thomas D.;  39;Gorman, William E.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Hodor, an intestinal zinc-gated chloride channel, controls systemic growth in Drosophila by promoting food intake and by modulating Tor signalling and lysosomal homeostasis within enterocytes.


In cells, organs and whole organisms, nutrient sensing is key to maintaining homeostasis and adapting to a fluctuating environment(1). In many animals, nutrient sensors are found within the enteroendocrine cells of the digestive system  however, less is known about nutrient sensing in their cellular siblings, the absorptive enterocytes(1). Here we use a genetic screen in Drosophila melanogaster to identify Hodor, an ionotropic receptor in enterocytes that sustains larval development, particularly in nutrient-scarce conditions. Experiments in Xenopus oocytes and flies indicate that Hodor is a pH-sensitive, zinc-gated chloride channel that mediates a previously unrecognized dietary preference for zinc. Hodor controls systemic growth from a subset of enterocytes-interstitial cells-by promoting food intake and insulin/IGF signalling. Although Hodor sustains gut luminal acidity and restrains microbial loads, its effect on systemic growth results from the modulation of Tor signalling and lysosomal homeostasis within interstitial cells. Hodor-like genes are insect-specific, and may represent targets for the control of disease vectors. Indeed, CRISPR-Cas9 genome editing revealed that the single hodor orthologue in Anopheles gambiae is an essential gene. Our findings highlight the need to consider the instructive contributions of metals-and, more generally, micronutrients-to energy homeostasis.


  
DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex 期刊论文
NATURE, 2020, 580 (7802) : 278-+
作者:  Wu, Thomas D.;  39;Gorman, William E.
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

The ID complex, involving the proteins FANCI and FANCD2, is required for the repair of DNA interstrand crosslinks (ICL) and related lesions(1). These proteins are mutated in Fanconi anaemia, a disease in which patients are predisposed to cancer. The Fanconi anaemia pathway of ICL repair is activated when a replication fork stalls at an ICL2  this triggers monoubiquitination of the ID complex, in which one ubiquitin molecule is conjugated to each of FANCI and FANCD2. Monoubiquitination of ID is essential for ICL repair by excision, translesion synthesis and homologous recombination  however, its function remains unknown(1,3). Here we report a cryo-electron microscopy structure of the monoubiquitinated human ID complex bound to DNA, and reveal that it forms a closed ring that encircles the DNA. By comparison with the structure of the non-ubiquitinated ID complex bound to ICL DNA-which we also report here-we show that monoubiquitination triggers a complete rearrangement of the open, trough-like ID structure through the ubiquitin of one protomer binding to the other protomer in a reciprocal fashion. These structures-together with biochemical data-indicate that the monoubiquitinated ID complex loses its preference for ICL and related branched DNA structures, and becomes a sliding DNA clamp that can coordinate the subsequent repair reactions. Our findings also reveal how monoubiquitination in general can induce an alternative protein structure with a new function.


Cryo-EM structures of the FANCI-FANCD2 complex bound to DNA reveal that monoubiquitination triggers structural changes that enable the complex to function as a sliding DNA clamp and coordinate the repair of DNA interstrand crosslinks.


  
Blocling alpha(4)beta(7) integrin binding to SIV does not improve virologic control 期刊论文
SCIENCE, 2019, 365 (6457) : 1033-+
作者:  Iwamoto, Nami;  Mason, Rosemarie D.;  Song, Kaimei;  Gorman, Jason;  Welles, Hugh C.;  Arthos, James;  Cicala, Claudia;  Min, Susie;  King, Hannah A. D.;  Belli, Aaron J.;  Reimann, Keith A.;  Foulds, Kathryn E.;  Kwong, Peter D.;  Lifson, Jeffrey D.;  Keele, Brandon F.;  Roederer, Mario
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
Laser cooling of ions in a neutral plasma 期刊论文
SCIENCE, 2019, 363 (6422) : 61-+
作者:  Langin, Thomas K.;  Gorman, Grant M.;  Killian, Thomas C.
收藏  |  浏览/下载:0/0  |  提交时间:2019/11/27
Changing available energy for extratropical cyclones and associated convection in Northern Hemisphere summer 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (10) : 4105-4110
作者:  Gertler, Charles G.;  39;Gorman, Paul A.
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27
climate change  available energy  extratropical cyclones  convection  
Trends in continental temperature and humidity directly linked to ocean warming 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (19) : 4863-4868
作者:  Byrne, Michael P.;  39;Gorman, Paul A.
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27
continental climate change  temperature  humidity  atmospheric dynamics  moisture transport  
Moist Formulations of the Eliassen-Palm Flux and Their Connection to the Surface Westerlies 期刊论文
JOURNAL OF THE ATMOSPHERIC SCIENCES, 2017, 74 (2)
作者:  Dwyer, John G.;  39;Gorman, Paul A.
收藏  |  浏览/下载:5/0  |  提交时间:2019/04/09
Kinetics and Mechanisms of Calcite Reactions with Saline Waters 科技报告
来源:US Department of Energy (DOE). 出版年: 2015
作者:  Gorman, Brian P
收藏  |  浏览/下载:0/0  |  提交时间:2019/04/05