Researchers have designed a three-dimensional model of an “average” synapse. This film shows various views of synapse organization, highlighting components such as the plasma membrane, cytosolic proteins, microtubles, actin, and septin. The camera later zooms in to show the synaptic vesicle and other features at higher resolution. Credit: Wilhelm et al. 2014, Science The following legend is also included in the movie frames: The synapse organization was modeled as described. Script (indicating approximate time intervals in minutes and seconds): 00:00 to 00:12 Lateral view of the synaptic bouton. Pink-colored protein is APP. The active zone area is shown by the fire-red shading. 00:12 to 00:24 Lateral view of the synaptic bouton, with the plasma membrane transparent. Red patches are formed by SNAP 25. 00:24 to 00:37 Lateral view of the synaptic bouton, without the plasma membrane lipids and proteins. The cytosolic proteins are visible. 00:37 to 00:42 All cytosolic proteins are removed, with the exception of synapsin (light green) and cytoskeletal elements: microtubules (brick-colored), actin (purple) and septin (moss-green) are visible. 00:43 to 00:53 Synapsin is also removed, to allow a view on the organelles and cytoskeleton. The mitochondrion outer membrane is shown in cream color. 00:54 onwards: Switching to a longitudinal section through the synapse. 00:54 to 00:57 All proteins are shown. 00:58 to 01:01 Synapsin is removed, but all other proteins are shown. 01:02 to 01:05 All cytosolic proteins but cytoskeletal elements are removed. 01:06 to 01:08 All organelles are removed. Only the plasma membrane, mitochondrion outer membrane and cytoskeleton are visible. 01:09 to 01:12 The cytoskeleton is removed as well. 01:13 to 01:17 The proteins involved in cargo delivery are shown. 01:17 to 01:21 The proteins involved in the retrieval of vesicle components are shown. 01:22 to 01:29 A view of the synapse without the cytosolic proteins. The organelles and the cytoskeleton are shown. The camera zooms onto a plasma membrane area at time 01:29. 01:29 to 01:39 Same view of the synapse. The camera moves towards a microtubule and an actin microfilament. 01:39 to 01:45 Same view of the synapse. The camera moves towards a synaptic vesicle. 01:45 to 01:48 Detailed view of the synaptic vesicle. See figure 5 for the legend for the different proteins. 01:49 to 01:52 The same synaptic vesicle is shown in presence of cytosolic proteins, with the exception of synapsin. 01:52 to 01:56 Synapsin, in light green, is also added. 01:57 to 02:05 The cytosolic proteins are again removed, and the camera moves towards the active zone. The active zone proteins are shown. Prominent are Munc13 (red), bassoon (cyan), Piccolo (brown). 02:06 to 02:12 The camera moves towards a vesicle in the process of endocytosis. 02:12 to 02:16 Clathrin molecules are added above the synaptic vesicle. 02:16 to 02:24 The camera moves above the active zone. Cytosolic proteins are shown only if they are within 100 nm from the plasma membrane, 02:24 to 02:28 All cytosolic proteins are added. The view of the synapse contains now all of the elements we analyzed. 02:28 to 02:35 The camera zooms out, and shows again the synapse view containing all proteins. (Movie S1 of 10.1126/science.1252884). - An Atomic View of Brain Activity news.sciencemag.org/biology/2014/05/video-atomic-view-brain-activity This, in all its molecular complexity, is what the bulging end of a single neuron looks like. A whopping 300,000 proteins come together to form the structure, which is less than a micrometer wide, hundreds of times smaller than a grain of sand. This particular synapse is from a rat brain. It’s where chemical signals called neurotransmitters are released into the space between neurons to pass messages from cell to cell. To create a 3D molecular model of the structure, researchers first isolated the synapses of rat neurons and turned to classic biochemistry to identify and quantify the molecules present at every stage of the neurotransmitter release cycle. Then, they used microscopy to pinpoint the location of each protein. Some proteins—like the red patches of SNAP25 visible in the video at 0:14—aid in the release of vesicles, tiny spheres full of neurotransmitters. Others—like the green, purple, and red rods at 0:45—help the synapse maintain its overall structure. Different proteins surround vesicles when they’re inside the synapse—the circles scattered throughout the structure at 0:56—than when the vesicles are forming at the edge of the synapse—as shown at 2:08. Researchers can use the model, described online today in Science, to better understand how neurons function and what goes wrong in brain disorders. - Researchers create highly detailed 3D model of an individual neural synapse medicalxpress/news/2014-05-highly-3d-individual-neural-synapse.html A team of researchers in Germany has created a very highly detailed 3D computer model of an individual rat synapse showing the distribution of approximately 30,000 proteins involved in the process of sending a message from one neuron to another. In their paper published in the journal Science, the team describes how they combined several imaging techniques to create the model, and what it is able to display. In simple terms, neurons transmit messages between one another via synapses—parts of neurons dedicated to converting electrical signals to chemical signals and vice versa. Synapses generally come in two varieties, the kind that send and the kind that receive signals. Neurons have both kinds of course, which allows them to send and receive messages. To send a message, electrical signals from the neuron travel to the sending synapse where they encounter vesicles. Prodded by the electrical signal, the vesicle releases chemicals called neurotransmitters into the space between (the cleft) the sending synapse on one neuron and the receiving synapse on another. The receiving synapse then processes the message and responds based on the signal it receives. In the sending synapse, the vesicles are made ready for action by being loaded with neurotransmitters and locked into position. Once they release their cargo, they are moved back out of the way so other vesicles can work while they are being refilled—once ready, they are again placed into position and put to use. This constant recycling goes on over and over, allowing neurons to process a steady stream of messages. In this new effort, the team in Germany has used a variety of microscopic methods to capture the structure of the sending synapse and what happens to it as recycling occurs and messages are sent. To create the model, the researchers isolated rat brain neurons and used mass spectrometry, electron microscopy, super-resolution fluorescence microscopy and antibody staining to get different looks at the sending synapse. In so doing they were able to determine the number of 62 different proteins involved in the recycling process and where they belong in the synapse. That allowed them to build a model able to depict how the synapse actually looks during each stage of the process—a feat that will undoubtedly help many other neuroscientists as they seek to better understand how the brain is able to do all the things it does. Reference Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins Science 30 May 2014: Vol. 344 no. 6187 pp. 1023-1028 DOI: 10.1126/science.1252884 sciencemag.org/content/344/6187/1023.abstract Editors Summary High-definition view of the synapse Individual neurons communicate with one another via their synapses, so to understand the nervous system, we need to understand in detail how the synapses are organized. Wilhelm et al. present a quantitative molecular-scale image of the “average” synapse populated with realistic renditions of each of the protein components that contribute to the inner workings of neurons. Science, this issue p. 1023 Abstract Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an “average” synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones. Supplementary Materials and Video sciencemag.org/content/suppl/2014/05/28/344.6187.1023.DC1/Wilhelm.SM.pdf
Posted on: Sun, 01 Jun 2014 20:55:33 +0000
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