Dan Wei and Nannan Gao contribute equally to this work, Dan Wei, Nannan Gao, Lei Li, Jing-Xiang Zhu, Lei Diao, Jiansong Huang, Qing-Jian Han, Shaogang Wang, Huaqing Xue, Qiong Wang, Qing-Feng Wu, Xu Zhang, Lan Bao, α-Tubulin Acetylation Restricts Axon Overbranching by Dampening Microtubule Plus-End Dynamics in Neurons, Cerebral Cortex, Volume 28, Issue 9, September 2018, Pages 3332â3346, https://doi.org/10.1093/cercor/bhx225. during the ________________ refractory period, another action potential can be generated, but only by a stimulus greater than the original. The neurons have only one axon, whose length can be up to 1m, but the axon can have bifurcations in a shape of axon projections. n = 28â34. the molecular changes that occur in long-term potentiation include which of the following? As for Axon, the benefits, compensation and infrastructure won't feel like a startup, but everything else will. Consistent with this, MEC-171â193 was able to partially rescue axon overbranching and overgrowth in MEC-17-deficient neurons. 5A, C), precluding significant changes to the actin cytoskeleton. To study whether loss of MEC-17 increases branch budding or decreases branch pruning, we performed time-lapse imaging to monitor the dynamic behavior of axon branching in cultured hippocampal neurons. INTRODUCTION. select all that apply. 1a-g). Maternal application of the α-tubulin deacetylase inhibitor tubacin rescues the neuronal migratory defect induced by silencing Srpx2 (Salmi et al. Axon termination is essential for efficient and accurate nervous system construction. These data rule out significant changes in microtubule-based axonal transport in MEC-17-deficient neurons. The activation of many muscle fibers together causes muscles to contract, which in turn can produce movement . 5DâF), similar to MEC-17F183A. Previous studies on the molecular structure of MEC-17 (Friedmann et al. Multiple forms of axon growth and synapse remodelling can restore function after injury and fall under the broad rubric of regeneration 3,4,5,6 (Fig. Post-translational modifications of tubulin may regulate the interaction between microtubule and microtubule-associated proteins or motor proteins, thereby controlling neuronal migration, synapse formation and neural network formation (Fukushima et al. Directly after isolation, plasmids were added to the suspension of neurons in Nucleofector buffer (0.1 mL), and the mixture was electroporated in an Amaxa Nucleofector II (Lonza) using program O-005. Taken together, MEC-17-mediated α-tubulin acetylation acts to maintain moderate microtubule bundling and dynamics in neuronal axons, especially at branch points and growth cones. which are true about action potentials? The microtubules in growth cones were imaged with a Leica TCS SP8 STED 3X super-resolution microscope (Leica). It possesses a nerve cell body, the perikaryon, from which, as mentioned above, a number of dendritic extensions and one axonal extension originate.As a result, this is the key feature of these nerve cells - a single axon and numerous processes. For quantitative analysis of EB3-RFP, approximately 10 neurons from each experiment and approximately 30 neurons from 3 independent experiments were collected for each group. select the four categories of neurotransmitters based on chemical composition. (B, C) Quantitative analysis of total axon length, number of axon branches, primary branches per 100 μm, axon branch length and longest axon length showed that the increases in axon branching and growth were rescued by the re-expression of MEC-17-GFP (B) and GFP-α-tubulinK40Q (C) but not of MEC-17F183A-GFP (B), MEC-17194â333-GFP (B) and GFP-α-tubulin (C) in MEC-17â/â neurons, and MEC-171â193-GFP (B) partially rescued the defects caused by MEC-17 deficiency. Given the pronounced correlation between axon overbranching and neuronal miswiring, behavioral abnormalities were expected in MEC-17-deficient mice. which factors influence the speed of nerve signal conduction? a single motor neuron stimulating hundreds of skeletal muscle cells is an example of which type of circuit? It then releases the neurotransmitters so neurons can communicate with one another. which term refers to this process? synapses are not fixed for life. Measurements are reported as mean ± SEM. 1EâG). A mutant deficient in acetyltransferase activity, MEC-17F183A, neither recovered the microtubule organization and hyperdynamics nor rescued the axonal defect in MEC-17-deficient neurons. Subsequently, neurons were plated with MEM containing 5% fetal bovine serum on 35-mm glass bottom dishes coated with poly-d-lysine (0.01 mg/mL, Sigma). Thus, taxol application suppresses the hyperdynamics of acetylation-deficient microtubules. Axon is a tube-like structure that carries electrical impulse from the cell body to the axon terminals that passes the impulse to another neuron. Collateral sprouts (red) form synaptic contact They bind neurons together and provide a supportive scaffold. n = 60â100 neurons from 3 to 4 experiments. labeled line coding depends on which of the following? In one axon collateral Musashi increases terminal arbors and directly or indirectly the synapse number by controlling pro-tein levels of Ptp69D through poly(A) tailing of its mRNA. which type of memory can store the most information? select two answers from the list below. The total contralateral branching shown in C was quantified and plotted as normalized values versus MEC-17+/+ mice. true or false: electrical synapses are able to integrate information and make decisions more rapidly than chemical signals. A cGMP signaling cascade composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2 (also known as GC-B or Npr-B . Here we extend this model by incorporating anatomically-inspired local inhibitory axon collateral networks into two basal ganglia nuclei (globus pallidus and substantia nigra pars reticulata). 2010; Li et al. MEC-17 deficiency induced anxiety-like behavior in mice. Axon branching is a fundamental mechanism in the development and repair of neuronal circuitry (Gibson and Ma, 2011; Onifer et al., 2011).The generation of axon collateral branches involves the coordinated reorganization of the actin filament and microtubule cytoskeleton (Dent and Kalil, 2001; Gallo, 2011; Kalil and Dent, 2014).However, how cytoskeletal dynamics are orchestrated . Indeed, the knockout mice displayed an anxiety-like behavior despite showing intact spatial learning and memory. inhibitory postsynaptic potential (IPSPs) maybe result from which of the following? This is a thorough revision of the standard text on local circuits in the different regions of the brain. In this fifth edition, the results of the mouse and human genome projects are incorporated for the first time. this region is an axon’s trigger zone, where action potentials are first produced if electrochemical events in the dendrites and/or cell body reach a threshold level. match the following terms with their description. 2C, D), suggesting that the increase in new branches is responsible for the excessive axon branching of neurons deficient in MEC-17. Loss of α-tubulin acetylation induced microtubule debundling and invasion as well as microtubule hyperdynamics in the axons of hippocampal neurons. Scale bar: 1 mm. Collaterals are fibers arising from the ____of neurons. a) convert blood glucose to lactate for neurons to use for fuel. The HEK293 cells were lysed in ice-cold RIPA buffer [150 mM NaCl, 10 mM Tris-HCl (pH 7.4), 1 mM EDTA, 0.1% Triton X-100, 10% glycerol, 0.1 mM PMSF, 1 mg/mL pepstatin A, and 1 mg/mL leupeptin]. this results in activation of many enzymes that induce gene transcription and thus, production of multiple metabolic products. Total fluorescence intensity of contralateral branching was normalized to the total area of labeled cell bodies to avoid the effects of variations in electroporation efficiency. The brains were dissected and post-fixed in the same fixative and then sequentially dehydrated in 20% and 30% sucrose at 4 °C overnight. helped the article revision. The origins of this book go back to the first electron microscopic studies of the central nervous system. Keywor: Cortical development, Axon guidance, Axon outgrowth, Axon collateral branching, Netrin-1, Atmospheric scanning electron microscopy 2010) provides a good tool to study the microtubule-related function of α-tubulin acetylation. The sections and cells were mounted and scanned using a Leica TCS SP5 or SP8 confocal microscope (Leica). 2010; Song et al. 1999; Orr et al. 1) degeneration of axon and myelin distal to injury. which would cause postsynaptic stimulation to end? 6AâD). **P < 0.01, ***P < 0.001 versus MEC-17+/+ , and ###P < 0.001 versus the indicated conditions. Entries into the light compartments were recorded. Scale bar: 200 μm. a shift in membrane voltage to a value that is more negative than the resting membrane potential is called _________________. It can make contact with the dendrite or cell body of another or the same neurons. The microtubule organization defects in MEC-17-deficient neurons, including increases in the total number of microtubule debundling sites in the axon, the number of microtubule debundling sites per 100 μm along the longest axon and the percentage of filopodia invaded by microtubules along the longest axon, were rescued by the application of 0.1 nM taxol (Fig. a) outward K+ diffusion causes positive and negative charges to accumulate on either side of the membrane where they attract each other, which three factors contribute the most to the formation of the negative resting membrane potential? 2. Impaired microtubule organization in the axons of MEC-17â/â hippocampal neurons could be rescued by re-expression of MEC-17-GFP but not of MEC-17F183A-GFP (D). Given that previously identified deacetylases, HDAC6 and SIRT2, deacetylate molecular substrates other than α-tubulin, the recent identification of the specific α-tubulin acetyltransferase MEC-17/αTAT-1 (α-tubulin acetyltransferase 1) (Akella et al. which type of memory is important as you read (e.g. A previous study also detected mild anxiety in MEC-17 knockout mice (Kalebic et al. Nerves that carry impulses from the heart to the brain could be classed as _____fibers. See also Supplementary Fig 1 and 2. L.D. Taken together, these data indicate that the effect of MEC-17 is specifically due to the regulation of α-tubulin acetylation. Then, the samples were incubated with specific Myc antibody-conjugated beads (Sigma) for 5 h at 4 °C. 3B, C). categorize the six kinds of neuroglia according to whether they are in the CNS or the PNS. These data further support a model in which MEC-17-mediated α-tubulin acetylation maintains moderate microtubule plus-end dynamics to keep the normal axon morphology. Hippocampal neurons were cultured for 48 h on glass bottom dishes and then placed on a temperature-controlled workstation (37 °C, 5% CO2) with an inverted microscope. which are usually found inside the cell body (or soma) of a mature neuron? 2015; Srivatsa et al. Address correspondence to Lan Bao, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China. 7B, C). the nervous system must interpret quantitative and qualitative information about its environment, thus it converts information to a meaningful pattern of action potentials. this is an example of which type of circuit? Previous studies have shown that the geometry, branching, and myelination pattern of an axon play an important role in determining the amplitude and duration of an action potential propagating along that axon. Neuronal morphology was analyzed using Neurolucida V9.0 (MBF Bioscience), Neurolucida Explorer V9.0 (MBF Bioscience), and ImageJ 1.46j (NIH). 2 E and F ), and the . The immunoreactive bands were quantified from 3 to 5 independent experiments using Image-Pro Plus 5.1 software. a) convert blood glucose to lactate for neurons to use for fuel b . Actin was labeled with Alexa Fluor 546 phalloidin (1:300; Invitrogen). 2013a) and that loss of MEC-17 makes microtubules more resistant to treatment with 10 μM nocodazole in mouse embryonic fibroblasts (Kalebic et al. 3B, C, and Supplementary Fig. how do neuromodulators after synaptic transmission? 2B), suggesting a higher density of axon branches. cells. Chemical manipulation to suppress microtubule plus-end dynamics rescues axon overbranching and overgrowth in MEC-17-deficient neurons. Scale bar: 5 μm. select all that apply. this process is called neural ________________. identify the major structures and functions of the nervous system in the maintenance of homeostasis. 4A, B), consistent with its weaker acetyltransferase activity than full-length MEC-17 (Fig. select all that apply. The detection of EB3-RFP in the axon shaft provides evidence of hyperdynamic microtubules in neurons with loss of MEC-17. Recently, we described the first neuronal function of MAP7 in regulating axon collateral branch development of rodent sensory neurons in the dorsal root ganglion (DRG) (Tymanskyj et al., 2017). The neurons were stained for α-tubulin (green), Ac-tubulin (red), and Tyr-tubulin (blue). α-Tubulin and GFP served as controls for protein loading and transfection, respectively. long-term potentiation may be involved in long-term memory. 3E). Axon collateral may divide into multiple smaller branches (telodendria: end branches) • At the end of each telodendrion is a knob called a terminal button, or end foot o Terminal button: sits close to but usually doesn't touch a dendritic spine or some other part of the cell. select all that apply. which numerical value is most likely to be the resting membrane potential of a neuron? J.X.Z., J.S.H., Q.J.H., S.G.W., Q.W., H.Q.X. Previous studies have reported that microtubule polymerization is required for axon branching (Letourneau et al. Journal of computational neuroscience, 16 (3), pp.211-235. E) synapse. (EâG) Quantitative analysis of branching distribution along the radial axis of the cortical wall showing significantly increased axon branching in ipsilateral layer 5 (E) and contralateral layers 2â3 and 5 (G) of somatosensory cortex. Neuron Types the sensory division of the PNS is further subdivided into the _______________ sensory division, which carries signals from receptors in the skin, muscles, bones and joints, and the _______________ sensory division, which carries signals from organs of the thoracic and abdominal cavities. enzyme amplification occurs at which type of synapse? The plasmids containing MEC-17-GFP and MEC-171â421-GFP with various truncations were constructed using PCR-amplified fragments inserted into the C-terminus of pEGFP-N3. The main function of the telodendria is to store vesicles that contain neurotransmitters. It is the chemical junction between the terminal of one neuron and dendrites of another neuron. Interestingly, in the open field test, MEC-17-deficient mice favored the peripheral area more than their wild-type littermates (Fig. The axon may be a single process, or it may have side branches called axon collaterals. 5I, J). GABA has an inhibitory effect on postsynaptic neurons because it does which of the following? It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Given that the collateral and terminal axon branching determines the wiring of a neural circuit in the brain, we wondered whether loss of MEC-17-mediated α-tubulin acetylation impairs the behavior of animals. All rights reserved. This book is a valuable resource for biologists, orthopedic surgeons, and neuroscientists. Two papers in this issue of Cell implicate ligands for receptor tyro- sine kinases of the Eph family as strong candidates for positional labels in the retinotectal system and suggest that graded spatial distributions of the factors on the factors are suggested in map formation. Data were quantified and plotted as normalized values versus MEC-17-GFP. We report that nerve growth factor (NGF), a branch‐inducing signal, increases the frequency of microtubule debundling along the axon shaft of chicken embryonic sensory neurons. A previous study reported that in the Atat1-001 isoform encoding MEC-17 with 421 aa (MEC-171â421), the sequence 307â387 aa is responsible for its interaction with α-tubulin (Montagnac et al. However, the mean staining intensity per axon and the distance of microtubule retraction from the growth cone after a high dose (5 μM) of nocodazole treatment for 5 or 30 min did not differ between MEC-17-deficient and wild-type neurons, suggesting an insignificant change in microtubule stability (Supplementary Fig. *P < 0.05 and ***P < 0.001, n = 4. which are functions of astrocytes? Xu Z, Schaedel L, Portran D, Aguilar A, Gaillard J, Marinkovich MP, Thery M, Nachury MV. The initiation and growth of axon branches require the regulation of cytoskeletal dynamics. select all that apply. Graphs showing dendritic diameter distribution as a function of the distance from soma in human (A) and mouse (B) for main apical dendrites (black), collateral dendrites (blue), basal dendrites (red), and axon (green). In the presence of MEC-17, α-tubulin acetylation keeps microtubules moderately dynamic and consolidated, and axon branching and growth are restricted during neuronal development. 2012b; Taschner et al. Finally, we demonstrate the potential connection be-tween branch development and reflex functions. 6EâH). Scale bar: 5 μm.
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