نتائج البحث - "Horvitz, H. Robert"

1

دورية أكاديمية

Additional file 1 of Deletion of VPS50 protein in mouse brain impairs synaptic function and behavior ...

المؤلفون: Ahumada-Marchant, Constanza, Ancatén-Gonzalez, Carlos, Haensgen, Henny, Brauer, Bastian, Merino-Veliz, Nicolas, Droste, Rita, Arancibia, Felipe, Horvitz, H. Robert, Constantine-Paton, Martha, Arriagada, Gloria, Chávez, Andrés E., Bustos, Fernando J.

مصطلحات موضوعية: Biophysics, Biochemistry, Medicine, Genetics, FOS Biological sciences, Molecular Biology, Neuroscience, Developmental Biology, Mental Health

الوصف: Additional file 1: Fig. S1. Cortical neurons were infected at 3 DIV with AVV encoding TdTomato as control and a combination of sgRNAs (1–6 / 2–4 / 1–4 / 2–6) targeting Vps50, as indicated. 10 days later genomic DNA was extracted, and the T7 endonuclease I assay was performed. (A) T7 endonuclease I assay for sgRNA combinations showing successful editing of the VPS50 locus with all sgRNA combinations as shown by lower size bands in the treated samples. (B) Sequences of VPS50 locus edited with sgRNAs in VPS50 KO cultured neurons showing the changes in the DNA sequence after gene editing using locus-specific sequencing. Fig S2. Proximity ligation assay (PLA) in Control and VPS50 KO neurons. PLA was performed using specific antibodies to determine proximity between proteins of interest. Low magnification (20x) for each condition are shown. Microtube-associated protein 2 (MAP2) was used to stain all neurons. (A) PLA for Synapsin1 (Syn1)-Synaptophysin (Syn) (pre-presynaptic) or (B) Synaptophysin-PSD95 (pre-post ...

الإتاحة: https://doi.org/10.6084/m9.figshare.26112963.v110.6084/m9.figshare.2611296310.3389/fncel.2014.0005810.1523/jneurosci.2335-16.201610.1016/j.cell.2019.12.03610.1038/nature1377210.1016/j.neuron.2011.05.00210.1097/gim.0b013e3181ff67ba10.1037/0894-4105.20.1.2110.1016/j.bbr.2012.12.01510.1093/hmg/ddr12210.1038/s41467-017-02716-510.1016/j.cub.2016.01.04910.1038/ncb312910.1016/j.devcel.2014.10.00710.1038/mp.2011.1010.1093/brain/awab20610.1038/nn.416110.1093/hmg/ddy42310.1146/annurev.neuro.26.041002.13141210.1074/jbc.m009451200Test
https://springernature.figshare.com/articles/journal_contribution/Additional_file_1_of_Deletion_of_VPS50_protein_in_mouse_brain_impairs_synaptic_function_and_behavior/26112963/1Test

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2

دورية أكاديمية

A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci

المؤلفون: Doi, Akiko, Suarez, Gianmarco D., Droste, Rita, Horvitz, H. Robert

المساهمون: U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences, Howard Hughes Medical Institute, Uehara Memorial Foundation, MEXT | Japan Society for the Promotion of Science

المصدر: Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: How cells regulate gene expression in a precise spatiotemporal manner during organismal development is a fundamental question in biology. Although the role of transcriptional condensates in gene regulation has been established, little is known about the function and regulation of these molecular assemblies in the context of animal development and physiology. Here we show that the evolutionarily conserved DEAD-box helicase DDX-23 controls cell fate in Caenorhabditis elegans by binding to and facilitating the condensation of MAB-10, the C. elegans homolog of mammalian NGFI-A-binding (NAB) protein. MAB-10 is a transcriptional cofactor that functions with the early growth response (EGR) protein LIN-29 to regulate the transcription of genes required for exiting the cell cycle, terminal differentiation, and the larval-to-adult transition. We suggest that DEAD-box helicase proteins function more generally during animal development to control the condensation of NAB proteins important in cell identity and that this mechanism is evolutionarily conserved. In mammals, such a mechanism might underlie terminal cell differentiation and when dysregulated might promote cancerous growth.

الإتاحة: https://doi.org/10.1038/s41467-023-42345-9Test
https://www.nature.com/articles/s41467-023-42345-9.pdfTest
https://www.nature.com/articles/s41467-023-42345-9Test

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3

دورية أكاديمية

Deletion of VPS50 protein in mouse brain impairs synaptic function and behavior.

المؤلفون: Ahumada-Marchant, Constanza, Ancatén-Gonzalez, Carlos, Haensgen, Henny, Brauer, Bastian, Merino-Veliz, Nicolas, Droste, Rita, Arancibia, Felipe, Horvitz, H. Robert, Constantine-Paton, Martha, Arriagada, Gloria, Chávez, Andrés E., Bustos, Fernando J.

المصدر: BMC Biology; 6/26/2024, Vol. 22 Issue 1, p1-18, 18p

مصطلحات موضوعية: SYNAPTIC vesicles, AUTISM spectrum disorders, NEUROPLASTICITY, CAENORHABDITIS elegans, DEVELOPMENTAL delay, NEURAL transmission

مستخلص: Background: The VPS50 protein functions in synaptic and dense core vesicle acidification, and perturbations of VPS50 function produce behavioral changes in Caenorhabditis elegans. Patients with mutations in VPS50 show severe developmental delay and intellectual disability, characteristics that have been associated with autism spectrum disorders (ASDs). The mechanisms that link VPS50 mutations to ASD are unknown. Results: To examine the role of VPS50 in mammalian brain function and behavior, we used the CRISPR/Cas9 system to generate knockouts of VPS50 in both cultured murine cortical neurons and living mice. In cultured neurons, KO of VPS50 did not affect the number of synaptic vesicles but did cause mislocalization of the V-ATPase V1 domain pump and impaired synaptic activity, likely as a consequence of defects in vesicle acidification and vesicle content. In mice, mosaic KO of VPS50 in the hippocampus altered synaptic transmission and plasticity and generated robust cognitive impairments. Conclusions: We propose that VPS50 functions as an accessory protein to aid the recruitment of the V-ATPase V1 domain to synaptic vesicles and in that way plays a crucial role in controlling synaptic vesicle acidification. Understanding the mechanisms controlling behaviors and synaptic function in ASD-associated mutations is pivotal for the development of targeted interventions, which may open new avenues for therapeutic strategies aimed at ASD and related conditions. [ABSTRACT FROM AUTHOR]

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النص الكامل

4

دورية أكاديمية

The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans

المؤلفون: Saul, Josh, Hirose, Takashi, Horvitz, H Robert

المساهمون: Massachusetts Institute of Technology. Department of Biology

المصدر: eLife

الوصف: Cell identity is characterized by a distinct combination of gene expression, cell morphology, and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here, we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in later larval stage and adult worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.

وصف الملف: application/pdf

العلاقة: eLife; https://hdl.handle.net/1721.1/146808Test; Saul, Josh, Hirose, Takashi and Horvitz, H Robert. 2022. "The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans." eLife, 11.

الإتاحة: https://hdl.handle.net/1721.1/146808Test

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5

دورية أكاديمية

Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids

المؤلفون: K., Dengke, Li, Zhijie, Lu, Alice Y, Sun, Fang, Chen, Sidi, Rothe, Michael, Menzel, Ralph, Sun, Fei, Horvitz, H Robert

المصدر: Cell. 161(5)

الوصف: Cells adapt to temperature shifts by adjusting levels of lipid desaturation and membrane fluidity. This fundamental process occurs in nearly all forms of life, but its mechanism in eukaryotes is unknown. We discovered that the evolutionarily conserved Caenorhabditis elegans gene acdh-11 (acyl-CoA dehydrogenase [ACDH]) facilitates heat adaptation by regulating the lipid desaturase FAT-7. Human ACDH deficiency causes the most common inherited disorders of fatty acid oxidation, with syndromes that are exacerbated by hyperthermia. Heat upregulates acdh-11 expression to decrease fat-7 expression. We solved the high-resolution crystal structure of ACDH-11 and established the molecular basis of its selective and high-affinity binding to C11/C12-chain fatty acids. ACDH-11 sequesters C11/C12-chain fatty acids and prevents these fatty acids from activating nuclear hormone receptors and driving fat-7 expression. Thus, the ACDH-11 pathway drives heat adaptation by linking temperature shifts to regulation of lipid desaturase levels and membrane fluidity via an unprecedented mode of fatty acid signaling.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0c9293msTest

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6

دورية أكاديمية

Cytochrome P450 Drives a HIF-Regulated Behavioral Response to Reoxygenation by C. elegans

المؤلفون: K., Dengke, Rothe, Michael, Zheng, Shu, Bhatla, Nikhil, Pender, Corinne L, Menzel, Ralph, Horvitz, H Robert

المصدر: Science. 341(6145)

الوصف: Oxygen deprivation followed by reoxygenation causes pathological responses in many disorders, including ischemic stroke, heart attacks, and reperfusion injury. Key aspects of ischemia-reperfusion can be modeled by a Caenorhabditis elegans behavior, the O2-ON response, which is suppressed by hypoxic preconditioning or inactivation of the O2-sensing HIF (hypoxia-inducible factor) hydroxylase EGL-9. From a genetic screen, we found that the cytochrome P450 oxygenase CYP-13A12 acts in response to the EGL-9-HIF-1 pathway to facilitate the O2-ON response. CYP-13A12 promotes oxidation of polyunsaturated fatty acids into eicosanoids, signaling molecules that can strongly affect inflammatory pain and ischemia-reperfusion injury responses in mammals. We propose that roles of the EGL-9-HIF-1 pathway and cytochrome P450 in controlling responses to reoxygenation after anoxia are evolutionarily conserved.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7mc6k017Test

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7

دورية أكاديمية

Presumptive TRP channel CED-11 promotes cell volume decrease and facilitates degradation of apoptotic cells in Caenorhabditis elegans

المؤلفون: Driscoll, Kaitlin, Stanfield, Gillian M., Droste, Rita, Horvitz, H. Robert

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2017 Aug . 114(33), 8806-8811.

الوصول الحر: https://www.jstor.org/stable/26487046Test

النص الكامل

8

دورية أكاديمية

H3.3 Nucleosome Assembly Mutants Display a Late-Onset Maternal Effect

المؤلفون: Burkhart, Kirk B, Sando, Steven R, Corrionero, Anna, Horvitz, H Robert

المساهمون: Howard Hughes Medical Institute, Massachusetts Institute of Technology. Department of Biology

المصدر: PMC

الوصف: © 2020 Elsevier Inc. Burkhart et al. show that mutants lacking components of H3.3 assembly complexes have pleiotropic defects that manifest near the onset of adulthood. Mitochondrial stress likely contributes to these late-onset defects. The late-onset defects of H3.3 assembly mutants can be maternally rescued.

وصف الملف: application/pdf

العلاقة: Current Biology; https://hdl.handle.net/1721.1/136022Test

الإتاحة: https://hdl.handle.net/1721.1/136022Test

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9

دورية أكاديمية

An hourglass circuit motif transforms a motor program via subcellularly localized muscle calcium signaling and contraction

المؤلفون: Sando, Steven R, Bhatla, Nikhil, Lee, Eugene LQ, Horvitz, H Robert

المصدر: eLife

الوصف: Neural control of muscle function is fundamental to animal behavior. Many muscles can generate multiple distinct behaviors. Nonetheless, individual muscle cells are generally regarded as the smallest units of motor control. We report that muscle cells can alter behavior by contracting subcellularly. We previously discovered that noxious tastes reverse the net flow of particles through the C. elegans pharynx, a neuromuscular pump, resulting in spitting. We now show that spitting results from the subcellular contraction of the anterior region of the pm3 muscle cell. Subcellularly localized calcium increases accompany this contraction. Spitting is controlled by an ‘hourglass’ circuit motif: parallel neural pathways converge onto a single motor neuron that differentially controls multiple muscles and the critical subcellular muscle compartment. We conclude that subcellular muscle units enable modulatory motor control and propose that subcellular muscle contraction is a fundamental mechanism by which neurons can reshape behavior.

وصف الملف: application/octet-stream

العلاقة: http://dx.doi.org/10.7554/elife.59341Test; eLife; https://hdl.handle.net/1721.1/135345.2Test

الإتاحة: https://doi.org/10.7554/elife.59341Test
https://hdl.handle.net/1721.1/135345.2Test

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النص الكامل

10

دورية أكاديمية

H3.3 Nucleosome Assembly Mutants Display a Late-Onset Maternal Effect

المؤلفون: Burkhart, Kirk B., Sando, Steven R., Corrionero, Anna, Horvitz, H. Robert

المساهمون: Life Sciences Research Foundation, Howard Hughes Medical Institute, National Institutes of Health

المصدر: Current Biology ; volume 30, issue 12, page 2343-2352.e3 ; ISSN 0960-9822

مصطلحات موضوعية: General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology

الإتاحة: https://doi.org/10.1016/j.cub.2020.04.046Test
https://api.elsevier.com/content/article/PII:S0960982220305601?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0960982220305601?httpAccept=text/plainTest

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