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Imbalanced protein homeostasis, such as excessive protein synthesis and protein aggregation, is a pathogenic hallmark of a range of neurological disorders. Here, using expression of mutant proteins, a knockdown approach and disease mutation knockin mice, we show that VCP (valosin-containing protein), together with its cofactor P47 and the endoplasmic reticulum (ER) morphology regulator ATL1 (Atlastin-1), regulates tubular ER formation and influences the efficiency of protein synthesis to control dendritic spine formation in neurons. Strengthening the significance of protein synthesis in dendritic spinogenesis, the translation blocker cyclohexamide and the mTOR inhibitor rapamycin reduce dendritic spine density, while a leucine supplement that increases protein synthesis ameliorates the dendritic spine defects caused by Vcp and Atl1 deficiencies. Because VCP and ATL1 are the causative genes of several neurodegenerative and neurodevelopmental disorders, we suggest that impaired ER formation and inefficient protein synthesis are significant in the pathogenesis of multiple neurological disorders.
Pubmed ID: 26984393 RIS Download
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsImaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
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View all literature mentionsOpen-access database of antibodies against human proteins developed through collaboration between Antibodypedia AB and the Nature Publishing Group. It aims to provide the scientific community and antibody distributors alike with information on the effectiveness of specific antibodies in specific applications--to help scientists select the right antibody for the right application. Antibodypedia's mission is to promote the functional understanding of the human proteome and expedite analysis of potential biomarkers discovered through clinical efforts. To this end, they have developed an open-access, curated, searchable database containing annotated and scored affinity reagents to aid users in selecting antibodies tailored to specific biological and biomedical assays. They envisage Antibodypedia as a virtual repository of validated antibodies against all human, and ultimately most model-organism, proteins. Such a tool will be exploitable to identify affinity reagents to document protein expression patterns in normal and pathological states and to purify proteins alone and in complex for structural and functional analyses. They hope to promote characterization of the roles and interplay of proteins and complexes in human health and disease. They encourage commercial providers to submit information regarding their inventory of antibodies with links to quality control data. Independent users can submit their own application-specific experimental data using standard validation criteria (supportive or non-supportive) developed with the assistance of an international advisory board recruited from academic research institutions. Users can also comment on specific antibodies without submitting validation data.
View all literature mentionsCell line COS-1 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.FVB-Tg(EIIa-cre)C5379Lmgd/J from IMSR.
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