Cerebellin precursor protein (Cbln1) is essential for synapse integrity in cerebellum through assembly into complexes that bridge pre-synaptic β-neurexins (Nrxn) to post-synaptic GluRδ2. However, GluRδ2 is largely cerebellum-specific, yet Cbln1 and its little studied family members, Cbln2 and Cbln4, are expressed throughout brain. Therefore, we investigated whether additional proteins mediate Cbln family actions. Whereas Cbln1 and Cbln2 bound to GluRδ2 and Nrxns1-3, Cbln4 bound weakly or not at all, suggesting it has distinct binding partners. In a candidate receptor-screening assay, Cbln4 (but not Cbln1 or Cbln2) bound selectively to the netrin receptor, (deleted in colorectal cancer (DCC) in a netrin-displaceable fashion. To determine whether Cbln4 had a netrin-like function, Cbln4-null mice were generated. Cbln4-null mice did not phenocopy netrin-null mice. Cbln1 and Cbln4 were likely co-localized in neurons thought to be responsible for synaptic changes in striatum of Cbln1-null mice. Furthermore, complexes containing Cbln1 and Cbln4 had greatly reduced affinity to DCC but increased affinity to Nrxns, suggesting a functional interaction. However, Cbln4-null mice lacked the striatal synaptic changes seen in Cbln null mice. Thus, Cbln family members interact with multiple receptors/signaling pathways in a subunit composition-dependent manner and have independent functions with Cbln4 potentially involved in the less well-characterized role of netrin/DCC in adult brain.
Pubmed ID: 22220752 RIS Download
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A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)
View all literature mentionsNeurolucida is advanced scientific software for brain mapping, neuron reconstruction, anatomical mapping, and morphometry. Since its debut more than 20 years ago, Neurolucida has continued to evolve and has become the worldwide gold-standard for neuron reconstruction and 3D mapping. Neurolucida has the flexibility to handle data in many formats: using live images from digital or video cameras; stored image sets from confocal microscopes, electron microscopes, and scanning tomographic sources, or through the microscope oculars using the patented LucividTM. Neurolucida controls a motorized XYZ stage for integrated navigation through tissue sections, allowing for sophisticated analysis from many fields-of-view. Neurolucidas Serial Section Manager integrates unlimited sections into a single data file, maintaining each section in aligned 3D space for full quantitative analysis. Neurolucidas neuron tracing capabilities include 3D measurement and reconstruction of branching processes. Neurolucida also features sophisticated tools for mapping delineate and map anatomical regions for detailed morphometric analyses. Neurolucida uses advanced computer-controlled microscopy techniques to obtain accurate results and speed your work. Plug-in modules are available for confocal and MRI analysis, 3D solid modeling, and virtual slide creation. The user-friendly interface gives you rapid results, allowing you to acquire data and capture the full 3D extent of neurons and brain regions. You can reconstruct neurons or create 3D serial reconstructions directly from slides or acquired images, and Neurolucida offers full microscope control for brightfield, fluorescent, and confocal microscopes. Its added compatibility with 64-bit Microsoft Vista enables reconstructions with even larger images, image stacks, and virtual slides. Adding the Solid Modeling Module allows you to rotate and view your reconstructions in real time. Neurolucida is available in two separate versions Standard and Workstation. The Standard version enables control of microscope hardware, whereas the Workstation version is used for offline analysis away from the microscope. Neurolucida provides quantitative analysis with results presented in graphical or spreadsheet format exportable to Microsoft Excel. Overall, features include: - Tracing Neurons - Anatomical Mapping - Image Processing and Analysis Features - Editing - Morphometric Analysis - Hardware Integration - Cell Analysis - Visualization Features Sponsors: Neurolucida is supported by MBF Bioscience.
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