Biology subjects

Wilson, M.

Publications and source records attributed to Wilson, M..

76 records · Page 5Linked to original sources

bioRxiv2018

Genetic and physical interactions between the organellar mechanosensitive ion channel homologs MSL1, MSL2, and MSL3 reveal a role for inter-organellar communication in plant development

Plant development requires communication on many levels, including between cells and between organelles within a cell. For example, mitochondria and plastids have been proposed to be sensors of environmental stress and to coordinate their responses. Here we present evidence for communication between mitochondria and chloroplasts during leaf and root development, based on genetic and physical interactions between three Mechanosensitive channels of Small conductance-Like (MSL) proteins from Arabidopsis thaliana. MSL proteins are Arabidopsis homologs of the bacterial Mechanosensitive channel of Small conductance (MscS), which relieves cellular osmotic pressure to protect against lysis during hypoosmotic shock. MSL1 localizes to the inner mitochondrial membrane, while MSL2 and MSL3 localize to the inner plastid membrane and are required to maintain plastid osmotic homeostasis during normal growth and development. In this study, we characterized the phenotypic effect of a genetic lesion in MSL1, both in wild type and in msl2 msl3 mutant backgrounds. msl1 single mutants appear wild type for all phenotypes examined. The characteristic leaf rumpling in msl2 msl3 double mutants was exacerbated in the msl1 msl2 msl3 triple mutant. However, the introduction of the msl1 lesion into the msl2 msl3 mutant background suppressed other msl2 msl3 mutant phenotypes, including ectopic callus formation, accumulation of superoxide and hydrogen peroxide in the shoot apical meristem, decreased root length, and reduced number of lateral roots. All these phenotypes could be recovered by molecular complementation with a transgene containing a wild type version of MSL1. In yeast-based interaction studies, MSL1 interacted with itself, but not with MSL2 or MSL3. These results establish that the abnormalities observed in msl2 msl3 double mutants is partially dependent on the presence of functional MSL1 and suggest a possible role for communication between plastid and mitochondria in seedling development.

plant biology↗

bioRxiv2018

Subtractive Interaction Proteomics Reveal a Network of Signaling Pathways Activated by an Oncogenic Transcription Factor in Acute Myeloid Leukemia

Acute myeloid leukemias (AML) are characterized by recurrent genomic alterations, often in transcriptional regulators, which form the basis on which current prognostication and therapeutic intervention is overlaid. In AML transformation can often be attributed to single chromosomal aberrations encoding oncogenes, such as t(15;17)-PML/RAR or t(6;9)-DEK/CAN but it is unclear how these aberrant transcription factors drive leukemic signaling and influence cellular responses to targeted therapies. Here we show that by using a novel \"subtractive interaction proteomics\" approach, the high risk AML-inducing oncogene t(6;9)-DEK/CAN directly activates signaling pathways that are driven by the ABL1, AKT/mTOR, and SRC family kinases. The interplay of these signaling pathways creates a network with nodes that are credible candidates for combinatorial therapeutic interventions. These results reveal specific interdependencies between nuclear oncogenes and cancer signaling pathways thus providing a foundation for the design of therapeutic strategies to better address the complexity of cancer signaling.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC=\"FIGDIR/small/464958_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (28K):\norg.highwire.dtl.DTLVardef@159295corg.highwire.dtl.DTLVardef@aa83d1org.highwire.dtl.DTLVardef@b41e11org.highwire.dtl.DTLVardef@122156e_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2018

Histone deacetylase activity is required for Botrylloides leachii whole body regeneration.

The colonial tunicate Botrylloides leachii is exceptional at regenerating from a piece of vascular tunic after loss of all adults from the colony. Previous transcriptome analyses indicate a brief period of healing before regeneration of a new adult (zooid) in as little as 8-10 days. However, there is little understanding of how the resulting changes to gene expression, required to drive regeneration, are initiated and how the overall process is regulated. Rapid changes to gene expression often occur in response to chromatin changes, mediated by histone modifications such as histone acetylation. Here, we investigated a group of key epigenetic modifiers, histone deacetylases (HDAC) that are known to play an important role in many biological processes such as development, healing and regeneration.\n\nThrough our transcriptome data, we identified and quantified the expression levels of HDAC and histone acetyltransferase (HAT) enzymes during whole body regeneration (WBR). To determine if HDAC activity is required for WBR, we inhibited its action using valproic acid (VPA) and Trichostatin A (TSA). HDAC inhibition prevented the final morphological changes normally associated with WBR and resulted in aberrant gene expression. B. leachii genes including Slit2, TGF-{square}, Piwi and Fzd4 all showed altered gene expression upon HDAC inhibition in comparison to the control samples. Additionally, atypical expression of Bl_Piwi was found in immunocytes upon HDAC inhibition.\n\nTogether, these results show that HDAC function, specifically HDAC I/IIa class enzymes, are vital for B. leachii to undergo WBR successfully.

molecular biology↗

bioRxiv2018

Social integration predicts mitochondrial DNA copy number in rhesus macaques

In many social mammals, social adversity predicts compromised health and reduced fitness. These effects are thought to be driven in part by chronic social stress, but their molecular underpinnings are not well understood. Recent work suggests that chronic stress can affect mitochondrial copy number, heteroplasmy rates, and function. Here, we tested the first two possibilities, for the first time in nonhuman primates. We manipulated dominance rank in captive female rhesus macaques (n=45), where low rank induces chronic social stress, and measured mitochondrial DNA copy number and heteroplasmy in five peripheral blood mononuclear cell types from each study subject. We found no effect of dominance rank on either mtDNA copy number or heteroplasmy rates. However, grooming rates, a measure of affiliative social behavior predicted by high social status, was positively associated with mtDNA copy number in B cells, cytotoxic T cells, and monocytes. Our results suggest that social interactions can influence mtDNA regulation in immune cells. Further, they indicate the importance of considering both affiliative and competitive interactions in investigating this relationship.

animal behavior and cognition↗