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Full-Text Articles in Medicine and Health Sciences
Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert
Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to localize there. Mitochondria from heart, skeletal muscle, brown adipose tissue, and …
Ephrin-B3 Controls Excitatory Synapse Density Through Cell-Cell Competition For Ephbs., Nathan T. Henderson, Sylvain J. Le Marchand, Martin Hruska, Simon Hippenmeyer, Liqun Luo, Matthew B. Dalva
Ephrin-B3 Controls Excitatory Synapse Density Through Cell-Cell Competition For Ephbs., Nathan T. Henderson, Sylvain J. Le Marchand, Martin Hruska, Simon Hippenmeyer, Liqun Luo, Matthew B. Dalva
Department of Neuroscience Faculty Papers
Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control …
Lactate-Mediated Epigenetic Reprogramming Regulates Formation Of Human Pancreatic Cancer-Associated Fibroblasts, Tushar D. Bhagat, Dagny Von Ahrens, Meelad Dawlaty, Yiyu Zou, Joelle Baddour, Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Brijesh Patel, Changsoo Kwak, Gaurav S. Choudhary, Shanisha Gordon-Mitchell, Srinivas Aluri, Sanchari Bhattacharyya, Srabani Sahu, Yiting Yu, Matthias Bartenstein, Orsi Giricz, Masako Suzuki, Davendra Sohal, Sonal Gupta, Paola A. Guerrero, Surinder K. Batra, Michael Goggins, Ulrich Steidl, John Greally, Beamon Agarwal, Kith Pradhan, Debabrata Banerjee, Deepak Nagrath, Anirban Maitra, Amit Verma
Lactate-Mediated Epigenetic Reprogramming Regulates Formation Of Human Pancreatic Cancer-Associated Fibroblasts, Tushar D. Bhagat, Dagny Von Ahrens, Meelad Dawlaty, Yiyu Zou, Joelle Baddour, Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Brijesh Patel, Changsoo Kwak, Gaurav S. Choudhary, Shanisha Gordon-Mitchell, Srinivas Aluri, Sanchari Bhattacharyya, Srabani Sahu, Yiting Yu, Matthias Bartenstein, Orsi Giricz, Masako Suzuki, Davendra Sohal, Sonal Gupta, Paola A. Guerrero, Surinder K. Batra, Michael Goggins, Ulrich Steidl, John Greally, Beamon Agarwal, Kith Pradhan, Debabrata Banerjee, Deepak Nagrath, Anirban Maitra, Amit Verma
Journal Articles: Biochemistry & Molecular Biology
Even though pancreatic ductal adenocarcinoma (PDAC) is associated with fibrotic stroma, the molecular pathways regulating the formation of cancer associated fibroblasts (CAFs) are not well elucidated. An epigenomic analysis of patient-derived and de-novo generated CAFs demonstrated widespread loss of cytosine methylation that was associated with overexpression of various inflammatory transcripts including CXCR4. Co-culture of neoplastic cells with CAFs led to increased invasiveness that was abrogated by inhibition of CXCR4. Metabolite tracing revealed that lactate produced by neoplastic cells leads to increased production of alpha-ketoglutarate (aKG) within mesenchymal stem cells (MSCs). In turn, aKG mediated activation of the …
Ca2+ Sensor Synaptotagmin-1 Mediates Exocytosis In Mammalian Photoreceptors, Justin J. Grassmeyer, Asia L. Cahill, Cassandra L. Hays, Cody Barta, Rolen M. Quadros, Channabasavaiah B. Gurumurthy, Wallace B. Thoreson
Ca2+ Sensor Synaptotagmin-1 Mediates Exocytosis In Mammalian Photoreceptors, Justin J. Grassmeyer, Asia L. Cahill, Cassandra L. Hays, Cody Barta, Rolen M. Quadros, Channabasavaiah B. Gurumurthy, Wallace B. Thoreson
Journal Articles: Pharmacology & Experimental Neuroscience
To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca2+ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous …