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Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca(2+) handling, we performed a chemical suppressor screen on zebrafish tremblor embryos, which suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the transfer of Ca(2+) from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+) sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and irregular contractions. We further show that overexpression of VDAC2 recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2 deficiency attenuates efsevin's rescue effect and that VDAC2 functions synergistically with MCU to suppress cardiac fibrillation in tremblor. Together, these findings demonstrate a critical modulatory role for VDAC2-dependent mitochondrial Ca(2+) uptake in the regulation of cardiac rhythmicity.
Pubmed ID: 25588501
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Web-service providing access to database that brings together information from broad range of resources. Web application for functional annotation and statistical hypothesis testing. Provides tools for analysis of genomic and microarray data. Collection of tools include Bibliographic Information,Databases,Gene Annotation,Gene Regulation, Microarray,Proteins,Sequence Manipulation - Nucleic Acids,Sequence Manipulation - Protein, Systems Biology.
View all literature mentionsA a configurable software package for peptide and protein mass spectrometry analyses. It includes the SEQUEST search algorithm to identify separate proteins in complex mixtures, interactive navigation tools to filter and sort protein summaries, customized spectral plots, and chromatograms using the PEPMATCH and PEPMAP tools. This software also has batch processing capabilities to improve throughput by queuing up several files, and custom-build proprietary databases, index databases, and retrieve databases through a public server.
View all literature mentionsSoftware used to compile images obtained from the Zeiss LSM 510 confocal microscope. The browser can be used for general image archiving and handling and interactive measurement in labs and workgroups. Features include orthogonal sectioning, 3D cut function, 3D view with calculation of single projections, and interactive measurement functions in the overlay dialog, such as scale bar, distance, and area.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
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