Blog
About

11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Oligodendrocytes (OLs) extend arborized processes that are supported by microtubules (MTs) and microfilaments. Little is known about proteins that modulate and interact with the cytoskeleton during myelination. Several lines of evidence suggest a role for 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) in mediating process formation in OLs. In this study, we report that tubulin is a major CNP-interacting protein. In vitro, CNP binds preferentially to tubulin heterodimers compared with MTs and induces MT assembly by copolymerizing with tubulin. CNP overexpression induces dramatic morphology changes in both glial and nonglial cells, resulting in MT and F-actin reorganization and formation of branched processes. These morphological effects are attributed to CNP MT assembly activity; branched process formation is either substantially reduced or abolished with the expression of loss-of-function mutants. Accordingly, cultured OLs from CNP-deficient mice extend smaller outgrowths with less arborized processes. We propose that CNP is an important component of the cytoskeletal machinery that directs process outgrowth in OLs.

          Related collections

          Most cited references 45

          • Record: found
          • Abstract: found
          • Article: not found

          RADIOAUTOGRAPHIC STUDIES OF CHOLINE INCORPORATION INTO PERIPHERAL NERVE MYELIN

          This radioautographic study was designed to localize the cytological sites involved in the incorporation of a lipid precursor into the myelin and the myelin-related cell of the peripheral nervous system. Both myelinating and fully myelinated cultures of rat dorsal root ganglia were exposed to a 30-min pulse of tritiated choline and either fixed immediately or allowed 6 or 48 hr of chase incubation before fixation. After Epon embedding, light and electron microscopic radioautograms were prepared with Ilford L-4 emulsion. Analysis of the pattern of choline incorporation into myelinating cultures indicated that radioactivity appeared all along the length of the internode, without there being a preferential site of initial incorporation. Light microscopic radioautograms of cultures at varying states of maturity were compared in order to determine the relative degree of myelin labeling. This analysis indicated that the myelin-Schwann cell unit in the fully myelinated cultures incorporated choline as actively as did this unit in the myelinating cultures. Because of technical difficulties, it was not possible to determine the precise localization of the incorporated radioactivity within the compact myelin. These data are related to recent biochemical studies indicating that the mature myelin of the central nervous system does incorporate a significant amount of lipid precursor under the appropriate experimental conditions. These observations support the concept that a significant amount of myelin-related metabolic activity occurs in mature tissue; this activity is considered part of an essential and continuous process of myelin maintenance and repair.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination.

            Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity.

               Liqun Luo (2001)
              The actin cytoskeleton plays a major role in morphological development of neurons and in structural changes of adult neurons. This article reviews the myriad functions of actin and myosin in axon initiation, growth, guidance and branching, in morphogenesis of dendrites and dendritic spines, in synapse formation and stability, and in axon and dendrite retraction. Evidence is presented that signaling pathways involving the Rho family of small GTPases are key regulators of actin polymerization and myosin function in the context of different aspects of neuronal morphogenesis. These studies support an emerging theme: Different aspects of neuronal morphogenesis may involve regulation of common core signaling pathways, in particular the Rho GTPases.
                Bookmark

                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                15 August 2005
                : 170
                : 4
                : 661-673
                Affiliations
                [1 ]Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
                [2 ]WEMB Biochem, Inc., Toronto, Ontario M9W 1E7, Canada
                [3 ]Institut de Recherches en Immunologie et Cancer, Université de Montréal, Montreal, Quebec H3C 3J7, Canada
                Author notes

                Correspondence to John Lee: johnlee@ 123456gene.com

                Article
                200411047
                10.1083/jcb.200411047
                2171497
                16103231
                Copyright © 2005, The Rockefeller University Press
                Categories
                Research Articles
                Article

                Cell biology

                Comments

                Comment on this article