scholarly journals Myosin II has distinct functions in PNS and CNS myelin sheath formation

2008 ◽  
Vol 182 (6) ◽  
pp. 1171-1184 ◽  
Author(s):  
Haibo Wang ◽  
Ambika Tewari ◽  
Steven Einheber ◽  
James L. Salzer ◽  
Carmen V. Melendez-Vasquez
Keyword(s):  
Nervous System ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Actin Polymerization ◽  
Myosin Ii ◽  
Myelin Formation ◽  
Sheath Formation ◽  
Central Nervous Systems ◽  
Glial Membrane ◽  
Cytoskeleton Dynamics

The myelin sheath forms by the spiral wrapping of a glial membrane around the axon. The mechanisms responsible for this process are unknown but are likely to involve coordinated changes in the glial cell cytoskeleton. We have found that inhibition of myosin II, a key regulator of actin cytoskeleton dynamics, has remarkably opposite effects on myelin formation by Schwann cells (SC) and oligodendrocytes (OL). Myosin II is necessary for initial interactions between SC and axons, and its inhibition or down-regulation impairs their ability to segregate axons and elongate along them, preventing the formation of a 1:1 relationship, which is critical for peripheral nervous system myelination. In contrast, OL branching, differentiation, and myelin formation are potentiated by inhibition of myosin II. Thus, by controlling the spatial and localized activation of actin polymerization, myosin II regulates SC polarization and OL branching, and by extension their ability to form myelin. Our data indicate that the mechanisms regulating myelination in the peripheral and central nervous systems are distinct.

scholarly journals Individual neuronal subtypes control initial myelin sheath growth and stabilization

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Heather N. Nelson ◽  
Anthony J. Treichel ◽  
Erin N. Eggum ◽  
Madeline R. Martell ◽  
Amanda J. Kaiser ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Myelin Sheath ◽  
Time Lapse ◽  
Marked Individual ◽  
Larval Zebrafish ◽  
Sheath Formation ◽  
Time Lapse Imaging

Abstract Background In the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Some contacts stabilize, leading to the initiation of axon wrapping, nascent myelin sheath formation, concentric wrapping and sheath elongation, and sheath stabilization or pruning by oligodendrocytes. Although axonal signals influence the overall process of myelination, the precise oligodendrocyte behaviors that require signaling from axons are not completely understood. In this study, we investigated whether oligodendrocyte behaviors during the early events of myelination are mediated by an oligodendrocyte-intrinsic myelination program or are over-ridden by axonal factors. Methods To address this, we utilized in vivo time-lapse imaging in embryonic and larval zebrafish spinal cord during the initial hours and days of axon wrapping and myelination. Transgenic reporter lines marked individual axon subtypes or oligodendrocyte membranes. Results In the larval zebrafish spinal cord, individual axon subtypes supported distinct nascent sheath growth rates and stabilization frequencies. Oligodendrocytes ensheathed individual axon subtypes at different rates during a two-day period after initial axon wrapping. When descending reticulospinal axons were ablated, local spinal axons supported a constant ensheathment rate despite the increased ratio of oligodendrocytes to target axons. Conclusion We conclude that properties of individual axon subtypes instruct oligodendrocyte behaviors during initial stages of myelination by differentially controlling nascent sheath growth and stabilization.

Fyn tyrosine kinase participates in the compact myelin sheath formation in the central nervous system

2000 ◽  
Vol 37 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Chika Seiwa ◽  
Ichiro Sugiyama ◽  
Takeshi Yagi ◽  
Taisen Iguchi ◽  
Hiroaki Asou
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tyrosine Kinase ◽  
Myelin Sheath ◽  
Sheath Formation ◽  
The Central Nervous System ◽  
Fyn Tyrosine Kinase

scholarly journals Polarization and Myelination in Myelinating Glia

2012 ◽  
Vol 2012 ◽  
pp. 1-28 ◽  
Author(s):  
Toshihiro Masaki
Keyword(s):  
Nervous System ◽  
Epithelial Cells ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Nerve Impulse ◽  
Membrane System ◽  
Cell Types ◽  
Cell Polarization ◽  
Polarization Study ◽  
Myelinating Glia

Myelinating glia, oligodendrocytes in central nervous system and Schwann cells in peripheral nervous system, form myelin sheath, a multilayered membrane system around axons enabling salutatory nerve impulse conduction and maintaining axonal integrity. Myelin sheath is a polarized structure localized in the axonal side and therefore is supposed to be formed based on the preceding polarization of myelinating glia. Thus, myelination process is closely associated with polarization of myelinating glia. However, cell polarization has been less extensively studied in myelinating glia than other cell types such as epithelial cells. The ultimate goal of this paper is to provide insights for the field of myelination research by applying the information obtained in polarity study in other cell types, especially epithelial cells, to cell polarization of myelinating glia. Thus, in this paper, the main aspects of cell polarization study in general are summarized. Then, they will be compared with polarization in oligodendrocytes. Finally, the achievements obtained in polarization study for epithelial cells, oligodendrocytes, and other types of cells will be translated into polarization/myelination process by Schwann cells. Then, based on this model, the perspectives in the study of Schwann cell polarization/myelination will be discussed.

scholarly journals Reappraisal of Human HOG and MO3.13 Cell Lines as a Model to Study Oligodendrocyte Functioning

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1096 ◽  
Author(s):  
Kim M. A. De Kleijn ◽  
Wieteke A. Zuure ◽  
Jolien Peijnenborg ◽  
Josje M. Heuvelmans ◽  
Gerard J. M. Martens
Keyword(s):  
Schwann Cells ◽  
Cell Lines ◽  
Myelin Sheath ◽  
Cultured Cells ◽  
In Vitro Models ◽  
Brain Functioning ◽  
Disease Mechanisms ◽  
Sheath Formation ◽  
Mrna Expression Levels

Myelination of neuronal axons is essential for proper brain functioning and requires mature myelinating oligodendrocytes (myOLs). The human OL cell lines HOG and MO3.13 have been widely used as in vitro models to study OL (dys) functioning. Here we applied a number of protocols aimed at differentiating HOG and MO3.13 cells into myOLs. However, none of the differentiation protocols led to increased expression of terminal OL differentiation or myelin-sheath formation markers. Surprisingly, the applied protocols did cause changes in the expression of markers for early OLs, neurons, astrocytes and Schwann cells. Furthermore, we noticed that mRNA expression levels in HOG and MO3.13 cells may be affected by the density of the cultured cells. Finally, HOG and MO3.13 co-cultured with human neuronal SH-SY5Y cells did not show myelin formation under several pro-OL-differentiation and pro-myelinating conditions. Together, our results illustrate the difficulty of inducing maturation of HOG and MO3.13 cells into myOLs, implying that these oligodendrocytic cell lines may not represent an appropriate model to study the (dys)functioning of human (my)OLs and OL-linked disease mechanisms.

scholarly journals Actin Filament Turnover Drives Leading Edge Growth during Myelin Sheath Formation in the Central Nervous System

2015 ◽  
Vol 34 (2) ◽  
pp. 139-151 ◽  
Author(s):  
Schanila Nawaz ◽  
Paula Sánchez ◽  
Sebastian Schmitt ◽  
Nicolas Snaidero ◽  
Mišo Mitkovski ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Actin Filament ◽  
Myelin Sheath ◽  
Leading Edge ◽  
Sheath Formation ◽  
The Central Nervous System

scholarly journals Individual neuronal subtypes control initial myelin sheath growth and stabilization

2019 ◽  
Author(s):  
Heather N. Nelson ◽  
Anthony J. Treichel ◽  
Erin N. Eggum ◽  
Madeline R. Martell ◽  
Amanda J. Kaiser ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Myelin Sheath ◽  
Time Lapse ◽  
Marked Individual ◽  
Larval Zebrafish ◽  
Sheath Formation ◽  
Time Lapse Imaging

AbstractBackgroundIn the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Some contacts stabilize, leading to the initiation of axon wrapping, nascent myelin sheath formation, concentric wrapping and sheath elongation, and sheath stabilization or pruning by oligodendrocytes. Although axonal signals influence the overall process of myelination, the precise oligodendrocyte behaviors that require signaling from axons are not completely understood. In this study, we investigated whether oligodendrocyte behaviors during the early events of myelination are mediated by an oligodendrocyte-intrinsic myelination program or are over-ridden by axonal factors.MethodsTo address this, we utilized in vivo time-lapse imaging in embryonic and larval zebrafish spinal cord during the initial hours and days of axon wrapping and myelination. Transgenic reporter lines marked individual axon subtypes or oligodendrocyte membranes.ResultsIn the larval zebrafish spinal cord, individual axon subtypes supported distinct nascent sheath growth rates and stabilization frequencies. Oligodendrocytes ensheathed individual axon subtypes at different rates during a two-day period after initial axon wrapping. When descending reticulospinal axons were ablated, local spinal axons supported a constant ensheathment rate despite the increased ratio of oligodendrocytes to target axons.ConclusionWe conclude that properties of individual axon subtypes instruct oligodendrocyte behaviors during initial stages of myelination by differentially controlling nascent sheath growth and stabilization.

scholarly journals Fluorescence-Based Analysis of Noncanonical Functions of Aminoacyl-tRNA Synthetase-Interacting Multifunctional Proteins (AIMPs) in Peripheral Nerves

Materials ◽  
2019 ◽  
Vol 12 (7) ◽  
pp. 1064
Author(s):  
Muwoong Kim ◽  
Hyosun Kim ◽  
Dokyoung Kim ◽  
Chan Park ◽  
Youngbuhm Huh ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Peripheral Nerves ◽  
Trna Synthetase ◽  
Ventral Horn ◽  
Nerve Degeneration ◽  
Aminoacyl Trna Synthetase ◽  
Multifunctional Proteins ◽  
Sheath Formation

Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs) are auxiliary factors involved in protein synthesis related to aminoacyl-tRNA synthetases (ARSs). AIMPs, which are well known as nonenzymatic factors, include AIMP1/p43, AIMP2/p38, and AIMP3/p18. The canonical functions of AIMPs include not only protein synthesis via multisynthetase complexes but also maintenance of the structural stability of these complexes. Several recent studies have demonstrated nontypical (noncanonical) functions of AIMPs, such as roles in apoptosis, inflammatory processes, DNA repair, and so on. However, these noncanonical functions of AIMPs have not been studied in peripheral nerves related to motor and sensory functions. Peripheral nerves include two types of structures: peripheral axons and Schwann cells. The myelin sheath formed by Schwann cells produces saltatory conduction, and these rapid electrical signals control motor and sensory functioning in the service of survival in mammals. Schwann cells play roles not only in myelin sheath formation but also as modulators of nerve degeneration and regeneration. Therefore, it is important to identify the main functions of Schwann cells in peripheral nerves. Here, using immunofluorescence technique, we demonstrated that AIMPs are essential morphological indicators of peripheral nerve degeneration, and their actions are limited to peripheral nerves and not the dorsal root ganglion and the ventral horn of the spinal cord.

scholarly journals GPR56/ADGRG1 regulates development and maintenance of peripheral myelin

2018 ◽  
Vol 215 (3) ◽  
pp. 941-961 ◽  
Author(s):  
Sarah D. Ackerman ◽  
Rong Luo ◽  
Yannick Poitelon ◽  
Amit Mogha ◽  
Breanne L. Harty ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Underlying Mechanism ◽  
Scaffolding Protein ◽  
Rodent Models ◽  
Myelin Thickness ◽  
Radial Sorting ◽  
Rhoa Signaling

Myelin is a multilamellar sheath generated by specialized glia called Schwann cells (SCs) in the peripheral nervous system (PNS), which serves to protect and insulate axons for rapid neuronal signaling. In zebrafish and rodent models, we identify GPR56/ADGRG1 as a conserved regulator of PNS development and health. We demonstrate that, during SC development, GPR56-dependent RhoA signaling promotes timely radial sorting of axons. In the mature PNS, GPR56 is localized to distinct SC cytoplasmic domains, is required to establish proper myelin thickness, and facilitates organization of the myelin sheath. Furthermore, we define plectin—a scaffolding protein previously linked to SC domain organization, myelin maintenance, and a series of disorders termed “plectinopathies”—as a novel interacting partner of GPR56. Finally, we show that Gpr56 mutants develop progressive neuropathy-like symptoms, suggesting an underlying mechanism for peripheral defects in some human patients with GPR56 mutations. In sum, we define Gpr56 as a new regulator in the development and maintenance of peripheral myelin.

Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors

2019 ◽  
Vol 25 (26) ◽  
pp. 2892-2905 ◽  
Author(s):  
Sumit Jamwal ◽  
Ashish Mittal ◽  
Puneet Kumar ◽  
Dana M. Alhayani ◽  
Amal Al-Aboudi
Keyword(s):  
Nervous System ◽  
Therapeutic Potential ◽  
The Body ◽  
Membrane Receptors ◽  
Physiological Importance ◽  
Physiological Processes ◽  
Central Nervous Systems ◽  
Energy Consuming ◽  
Metabolic Dysfunctions ◽  
G Protein Coupled

Adenosine is a naturally occurring nucleoside and an essential component of the energy production and utilization systems of the body. Adenosine is formed by the degradation of adenosine-triphosphate (ATP) during energy-consuming processes. Adenosine regulates numerous physiological processes through activation of four subtypes of G-protein coupled membrane receptors viz. A1, A2A, A2B and A3. Its physiological importance depends on the affinity of these receptors and the extracellular concentrations reached. ATP acts as a neurotransmitter in both peripheral and central nervous systems. In the peripheral nervous system, ATP is involved in chemical transmission in sensory and autonomic ganglia, whereas in central nervous system, ATP, released from synaptic terminals, induces fast excitatory postsynaptic currents. ATP provides the energetics for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. Adenosine has been traditionally considered an inhibitor of neuronal activity and a regulator of cerebral blood flow. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosinerelated drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases. This review will summarize the therapeutic potential and recent SAR and pharmacology of adenosine and its receptor agonists and antagonists.

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