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During development of the peripheral nervous system in mammals, Schwann cells wrap their plasma membranes around neuronal axons, forming multiple myelin sheaths. A mature myelin sheath insulates axons and increases nerve conduction velocity while protecting nerve fibers from various stresses such as physical ones. Despite this functional importance, the molecular units that underlie dynamic morphological changes in formation of myelin sheaths are not sufficiently understood. Arf1 is a small guanosine triphosphate-binding protein that plays multiple roles in intracellular trafficking and related signaling, both of which are processes involved in cell morphogenesis. We demonstrate that the Arf1 guanine nucleotide exchange factor, brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1)/Arfgef1, and the effector Arf1 regulate the initiation of myelination of axons by Schwann cells. Schwann cell-specific BIG1 conditional knockout mice, which have been generated here, exhibit reduced myelin thickness and decreased localization of myelin protein zero in the myelin membrane, compared with their littermate controls. BIG1 knockout mouse nerves specifically decrease the amounts of Arf1 in the AP1 clathrin adaptor protein subunits but not the Arf1 binding to GGA1 (Golgi-localized, gamma-adaptin ear-containing, Arf-binding protein 1) transporting proteins. The amounts of Arf1 in the COPI coatomer protein subunits were comparable in the knockout mice and controls. Similar results in myelin thickness are observed in Arf1 conditional knockout mice, which have also been generated here. Thus, the BIG1 and Arf1 unit plays a key role in Schwann cell myelination, newly adding it to the list of molecular units controlling myelination.
Pubmed ID: 29740613
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A commercial antibody supplier and provider of various services.
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 11, 2023. Web tool for an organized view of the transcriptome. Collection of the computationally identified transcripts from the same locus. Information on protein similarities, gene expression, cDNA clones, and genomic location. System for automatically partitioning GenBank sequences into a non redundant set of gene oriented clusters.
View all literature mentionsDigitizer software which can convert graph images to useful (x,y) data by turning a scanner into an automatic graph digitizer. UN‑SCAN‑IT works with most image formats (TIFF, JPG, BMP, GIF, etc.) from any scanner, digital camera, or other image source to digitize plots, instrumental output, published graphs, etc. Its features include: automatically digitizing strip chart and xy recorder output, digitizing graphs that are on different scales to compare results, comparing data with published graphs of other investigators, digitizing old plots and charts for comparison with new data, and re‑scaling and appending existing printed graphs.
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsCenter that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsMus musculus with name C57BL/6N-Atm1Brd Arf1tm1a(EUCOMM)Wtsi/BayMmucd from MMRRC.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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