axonal membrane function

Neurosci. (2005). Blood Flow Metab. A., Jones, I. R., Ruderfer, D. M., Jones, L., et al. doi: 10.1101/cshperspect.a020495. Studies have shown that the first Zu5 domain of ankyrin is the canonical β-spectrin binding site since this is where βII-spectrin binds to ankyrin-B in neonatal cardiomyocytes and where βI-spectrin binds to ankyrin-R in erythrocytes (Mohler et al., 2004; Ipsaro and Mondragon, 2010; Ipsaro et al., 2010). 17, 1673–1681. The cell body (soma) is the factory of the neuron.It produces all the proteins for the dendrites, axons and synaptic terminals and contains specialized organelles such as the mitochondria, Golgi apparatus, endoplasmic reticulum, secretory granules, ribosomes and polysomes to provide energy and make the parts, as well as a production line to assemble the parts into completed … Myelination divides the axonal membrane into distinct domains including nodes of Ranvier, paranodes, juxtaparanodes and internodes. Am. Bréchet, A., Fache, M. P., Brachet, A., Ferracci, G., Baude, A., Irondelle, M., et al. 143, 1295–1304. doi: 10.1016/s0896-6273(01)00306-3, Petersen, J. D., Kaech, S., and Banker, G. (2014). doi: 10.1016/j.semcdb.2010.10.001, Craner, M. J., Newcombe, J., Black, J. (2006). The structure and chemical properties of the axon membrane is what enables it to contain an electrical charge, to force its flow in one direction, and to transfer the signal to other cells of the body. For the most part, for most types of nerve cells, the axon is insulated within a protective sheath called myelin. doi: 10.1038/nature09160, Gutzmann, A., Ergül, N., Grossmann, R., Schultz, C., Wahle, P., and Engelhardt, M. (2014). doi: 10.1074/jbc.271.49.31391, Zhang, X., and Bennett, V. (1998). doi: 10.7554/eLife.04581, Zhou, D. X., Lambert, S., Malen, P. L., Carpenter, S., Boland, L. M., and Bennett, V. (1998). Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals interaction surfaces necessary for ankyrin function. Post-mortem brains of schizophrenic patients revealed a 15%–20% decrease in ankyrin-G expression at the AIS of pyramidal neurons in the superficial cortical layer as compared to neurotypical controls, while no significant changes in AIS length were observed (Cruz et al., 2009). The structure and chemical properties of the axon membrane is what enables it to contain an electrical charge, to force its flow in one direction, and to transfer the signal to other cells of the body. A recent study quantitatively sought to determine the nanoscale organization of the AIS using Stochastic Optical Reconstruction Microscopy (STORM). No Pasaran! These data show that increasing the affinity of ion channels for ankyrin-G is an important regulatory step in the formation of the AIS. doi: 10.1523/JNEUROSCI.0277-13.2013, Fache, M. P., Moussif, A., Fernandes, F., Giraud, P., Garrido, J. J., and Dargent, B. Cell Biol. J. Biol. 12:e1006457. Nav1.1 is predominantly expressed in nodes of Ranvier and axon initial segments. In humans, axons may be more than a meter long, yet it takes only a few milliseconds for an action potential to move along their length. J. Nakada et al. PLoS Genet. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Polyarteritis Nodosa (PAN; Systemic Necrotizing Vasculitis). Cell. Nat. Versican V2 assembles the extracellular matrix surrounding the nodes of ranvier in the CNS. Diffuse Axonal Injury [edit | edit source] The primary insult of axonal injury leads to disconnection and/or neuron connections malfunction resulting in functional areas impairment. These changes in the AIS perhaps highlight a potential mechanism underlying mild traumatic brain injury and future studies will be important to elucidate the specific molecular components that contribute to the structural and functional changes in the AIS. Consistent with this idea, genome-wide association studies have identified ANK3 as one of the most significant risk loci for bipolar disorder, and to a lesser degree schizophrenia (Ferreira et al., 2008; Muhleisen et al., 2014; Roussos and Haroutunian, 2014). doi: 10.1038/nn2040, Kole, M. H., and Stuart, G. J. The complex organization of the Nodes of Ranvier is accomplished in part by myelinating Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). doi: 10.1212/01.wnl.0000275229.13012.32, Dzhashiashvili, Y., Zhang, Y. Q., Galinska, J., Lam, I., Grumet, M., and Salzer, J. L. (2007). 8:11. doi: 10.3389/fnana.2014.00011, Hamada, M. S., and Kole, M. H. (2015). Passive Axon Tutorial 2007 How voltages spread in axons and dendrites without voltage-sensitive channels (cable theory) From the experiments in this tutorial on the passive decay of a voltage along the axon (shown with 4 recording locations in the diagram below), you will see the necessity for a mechanism to enhance the voltage spread for long distance signaling. J. Neurosci. doi: 10.1523/JNEUROSCI.4314-05.2006, Pedraza, L., Huang, J. K., and Colman, D. R. (2001). J. Hum. (2016) showed that the presence of a bipolar disorder-associated variant in ANK3 results in reduced expression of the ANK3 exon 1b isoform in the AIS of parvalbumin-positive (PV) GABAergic interneurons. This is particularly important in the brain, where a single electrical impulse can stimulate multiple other neurons. Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. (2004). Rev. Neurol. The function of neurons is that they process incoming signals and act as the control unit. (2012). 569, 801–816. J. Neurosci. This striking plasticity of the AIS arises in an attempt to maintain homeostasis within individual neurons and balance synchronization between complex neuronal circuits. Recent studies by Ho et al. Axonal excitability studies allow deductions about membrane and ion channel properties in vivo. (2016). Bilaterian giant ankyrins have a common evolutionary origin and play a conserved role in patterning the axon initial segment. 177, 857–870. (2017). The distribution and targeting of neuronal voltage-gated ion channels. Ankyrin G membrane partners drive the establishment and maintenance of the axon initial segment. 79, 209–217. (2014) discovered that in the absence of ankyrin-G, Nav channels are still clustered to the node of Ranvier by compensation of ankyrin-R and its binding partner βI-spectrin in peripheral sensory neurons and retinal ganglion cells. doi: 10.1038/ng.209, Fjell, J., Hjelmstrom, P., Hormuzdiar, W., Milenkovic, M., Aglieco, F., Tyrrell, L., et al. Learn about a little known plugin that tells you if you're getting the best price on Amazon. Future research should expand on these findings to better understand how deletion of ankyrin-G or neurofascin disrupts Nav clustering throughout CNS, and how this loss of Nav channels at the node impacts brain function. (2016). Kv channels at the node include Kv3.1b, KCNQ2 and KCNQ3 (Cooper, 2011). Physiologists, biochemists, pharmacologists, cell biologists, neurologists, and neuropathologists who would like to find out more and make a study about the node of Ranvier will find the text helpful and relevant. Its main body, called the soma, generates an electrical pulse. doi: 10.1113/jphysiol.2005.097022, Palay, S. L., Sotelo, C., Peters, A., and Orkand, P. M. (1968). U S A 99, 17072–17077. Ann. The integrity and health of the axon membrane are known to be one of the keys to debilitating neurological diseases, such as Multiple Sclerosis (MS). βII-spectrin becomes enriched in a periodic arrangement in the AIS very early in development, before the other AIS proteins are detectable, and then migrates to more distal regions within the axon. doi: 10.1038/nrn2852, Rasband, M. N., and Peles, E. (2015). doi: 10.1016/j.ajhg.2015.01.010, Jacobson, C., Schnapp, B., and Banker, G. A. 151, 985–1002. Davis, L., Abdi, K., Machius, M., Brautigam, C., Tomchick, D. R., Bennett, V., et al. Instead, deletion of ankyrin-B results in shortened axonal tracts and impaired axonal transport due to the loss of ankyrin-B association with dynactin and dynein mediated cargo transport (Lorenzo et al., 2014). Hyperpolarising makes the neuron membrane more negative. 26, 5230–5239. Axon initial segments: diverse and dynamic neuronal compartments. The present study investigated changes in excitability in ipsilateral and contralateral upper limb peripheral motor axons in patients with acute cerebellar … LIS1 has been shown to be an important regulator of NDEL1-based dynein activity at the AIS (Vallee and Tsai, 2006). doi: 10.1038/nrn1938. 11, 552–562. 207, 735–752. In support of this view, experiments using fluorescently-labeled mutant kinesin motors were conducted to monitor which subtypes of kinesin motors translocate to either dendritic or axonal domains (Nakata et al., 2011). Cell. Cell 149, 525–537. Acad. (2008) showed that CK2 phosphorylation of various serine residues (S1112, S1124 and S1126) and a glutamate residue (E1111) on Nav1.2 regulates Nav channel association with ankyrin-G. Acad. More work is necessary to determine the precise mechanisms by which ankyrin-G recruits βIV-spectrin to the AIS. That signal travels through a long, thin extension called its axon. Chem. What Is the Role of Action Potential in Muscles. We conclude that logical features (Grace and Onn, 1989; Yung et al., 1991). Neuron 47, 215–229. The authors also identified a critical serine residue located within the giant exon, but outside of the canonical binding site of βIV-spectrin, that regulates spectrin localization via a likely phosphorylation-dependent mechanism. 290, 16619–16632. Sodium channel beta subunits: emerging targets in channelopathies. Interestingly, however, the axonal process eventually excludes MAP2 and acquires the axonal marker, neurofilament, despite a complete lack of the AIS. Few details are known, however, about the targeting … The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Role of the axon initial segment in the regulation of protein transport and the maintenance of axonal identity. doi: 10.1523/JNEUROSCI.5434-11.2012, Grubb, M. S., and Burrone, J. doi: 10.1016/b978-0-444-63326-2.00005-3, Susuki, K., Chang, K. J., Zollinger, D. R., Liu, Y. H., Ogawa, Y., Eshed-Eisenbach, Y., et al. Oligodendrocytes and Schwann cells are highly specialized glial cells that wrap axons with a multilayered myelin membrane for rapid impulse conduction. One function of the initial segment is to separate the main part of an axon from the rest of the neuron; another function is to help initiate action potentials. (2006). The knockdown of ankyrin-G, NDEL1, or LIS1 results in the entry of dendritic cargo into the proximal axon, thus these findings suggest a “quick-switch” mechanism for selective vesicle filtering at the AIS. Here we will cover the mechanisms of formation and maintenance of these axonal excitable membrane domains, specifically highlighting the similarities and differences between them. Scientists studying the molecular structure of the membrane and the chemical composition of synapses now understand that the signal transfer is actually a chemical one. 12, 568–576. 1 Electrochemical events in the cell body summate in the axon hillock, and the effect are directly passed to the attached axon. 2 If an action potential is generated, the axon conducts it away from the cell body. 3 The axon attaches directly to the dendrites in some neurons. ... More items... U S A 101, 8168–8173. A functional barrier to movement of lipids in polarized neurons. These data demonstrate that the AIS is critical for maintaining axonal identity in the proximal axon, but also that a transition from dendritic to axonal character can occur in an ankyrin-G and AIS-independent manner. Cell 33, 692–703. From axon to dendrites, the signal traverses a tiny gap between them called a synapse. (2010). Glia 64, 1190–1209. The AIS is a specialized membrane domain approximately 10–60 μm long and is generally located at the most proximal region of the axon (Palay et al., 1968). 181, 1169–1177. Genet. Dynein regulator NDEL1 controls polarized cargo transport at the axon initial segment. Neurosci. doi: 10.1016/j.ajhg.2010.04.013, Schafer, D. P., Custer, A. W., Shrager, P., and Rasband, M. N. (2006). 380, 32–36. NgR(310)ecto-Fc promotes corticospinal and raphe-spinal growth and functional recovery after SCI in rats (Li et al. Axonal and somatodendritic Gal‐4 is indicated with arrows and arrowheads respectively. Despite the fact that βIV-spectrin can interact with αII-spectrin (Uemoto et al., 2007); αII-spectrin has not yet been identified at the AIS. Res. Emergent complexities revealed in this volume compel a major revision in the traditional conceptual model of the axon’s intrinsic makeup and capacities. doi: 10.1146/annurev-neuro-062111-150339. Funct. By continuing you agree to the use of cookies. doi: 10.1016/j.ajhg.2010.07.019, Baalman, K. L., Cotton, R. J., Rasband, S. N., and Rasband, M. N. (2013). Despite similar structural composition between the AIS and the nodes, the mechanisms by which these microdomains form are quite different. As a result, the outer surface of the axonal membrane possesses a positive charge while its inner surface Figure 21.1 Structure of a neuron Nerve excitability techniques, recently adapted for clinical use (12–14), provide information about axonal membrane ion channel function. Acad. Interestingly, mice lacking the exon 1b isoform loose Nav channel clustering at the AIS of PV interneurons and demonstrate behavioral characteristics of bipolar disorder, epilepsy and sudden death (Lopez et al., 2016). In this case, the stimuli elicits an action potential at one point. Thus, mutations within ANK2 or ANK3 may lead to abnormalities in the AIS and axonal nodes of Ranvier as well as the paranodes within glia. 284, 6982–6987. Physiol. AnkyrinG is required to maintain axo-dendritic polarity in vivo. Microtubule stabilization specifies initial neuronal polarization. Acad. doi: 10.1083/jcb.200610128, Yoshimura, T., and Rasband, M. N. (2014). STED nanoscopy reveals the ubiquity of subcortical cytoskeleton periodicity in living neurons. Future studies need to evaluate additional AIS-independent mechanisms and how they may be critical to establish and maintain distinct axonal and dendritic polarized compartments. 270, 2352–2359. Cell Biol. A strength of Concepts of Biology is that instructors can customize the book, adapting it to the approach that works best in their classroom. Impact Factor 5.505 | CiteScore 7.0More on impact ›, Neurobiology of the Axon in Health and Disease Further, live-imaging experiments demonstrated that vesicles containing dendritic cargo enter the axon and dendrites with equal frequency; however, once inside the AIS the vesicles with dendritic proteins reverse directions and proceed toward the somatodendritic domain via an actin and myosin Va-dependent mechanism, whereas vesicles with axonal proteins proceed efficiently down the axon (Al-Bassam et al., 2012). In mammals, although β-spectrins are encoded by five different genes, only βIV-spectrin is found to be enriched at the AIS and nodes of Ranvier, and its recruitment to these sites depends on the direct interaction with ankyrin-G (Yang et al., 2007). Cell Biol. J. Neurosci. Neuron 49, 797–804. Proc. doi: 10.1083/jcb.143.5.1295, Zonta, B., Tait, S., Melrose, S., Anderson, H., Harroch, S., Higginson, J., et al. Actin gives strength to the bending and shape changing of the membrane when a new dendrite or axon is growing. Glial ankyrins facilitate paranodal axoglial junction assembly. Med. An electrical charge applied to an axon that moves the membrane potential from -70 mV to -45 mV will result in a(n) action potential. Summary of axonal functions. Structural and functional plasticity at the Axon initial segment. (2012). 204, 2363–2372. J. Biol. The establishment of polarity by hippocampal neurons in culture. Nat. The molecular composition of the nodes of Ranvier and the AIS are very similar in that they both consist of similar ion channels, cell adhesion molecules and scaffolding proteins (Figure 4; Rasband, 2010). Figure 2. The intricate formation and function of excitable axonal microdomains of the vertebrate nervous system plays a critical role in fast neuronal signaling and higher order cognitive processing. Neurosci. The migration of βII-spectrin down the axon coincides with the appearance of ankyrin-G and βIV-spectrin at the AIS (Zhong et al., 2014). Chem. Which way to go? The phosphorylation state of the FIGQY tyrosine of neurofascin determines ankyrin-binding activity and patterns of cell segregation. 6, 201–214. J. Neurosci. NgR1 function can be blocked by a soluble form of extracellular NgR1 fused to human Fc (NgR(310)ecto-Fc). Further Development 15.11: Turning the Growth Cone Requires Membrane Endocytosis Neural Crest Cells and Axonal Specificity Further Development 15.12: The Classic Example of Semaphorin-Mediated Repulsion of the Grasshopper Sensory Axon 4:e1000317. In addition, mutation of the ankyrin-G-binding domain in NF186 inhibits its ability to cluster at the node (Susuki et al., 2013). Pathogenesis of axonal and neuronal damage in multiple sclerosis. The complement of Nav and Kv channels at the node are diverse and can include Nav1.1, Nav1.2, Nav1.6, Nav1.7, Nav 1.8 and Nav1.9 which interact with β-subunits Navβ1, Navβ2 and Navβ4 (Fjell et al., 2000; Chen et al., 2002; Boiko et al., 2003; Henry et al., 2005; Duflocq et al., 2008; Black and Waxman, 2012). Neurosci. While phosphorylation is necessary to assemble and maintain proper AIS structure and function, the Ca2+-dependent cysteine protease calpain works in opposition to promote the degradation and disassembly of the AIS. Found insideThis book introduces the reader to the latest discoveries and concepts of neuronal migration enabled through the application of most sophisticated methods and cutting edge experimental approaches. The DENDRITES of a neuron are short extensions of the cell body that greatly increase the surface area of the cell. This recording of the axonal membrane potential in a presynaptic neuron shows that it is generating Action potentials move rapidly, at speeds up to 100 meters per second. (2001). Protein kinase CK2 contributes to the organization of sodium channels in axonal membranes by regulating their interactions with ankyrin G. J. A single, microscopic axon thread in the human body can be short, but it can also be 4.9 feet long (1.5 meters) or more. Local currents induce depolarisation of the adjacent axonal membrane and where this reaches a threshold, further action potentials are generated.
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