Nodes of Ranvier form in association with ezrin-radixin-moesin (ERM)-positive Schwann cell processes

Melendez‐Vasquez, Carmen V.; Rios, Jose C.; Zanazzi, George; Lambert, Stephen; Bretscher, Anthony; Salzer, James L.

doi:10.1073/pnas.98.3.1235

Cited by 116 publications

(120 citation statements)

References 36 publications

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“…In control cocultures, ezrin was clearly concentrated at the ends of myelinated segments (Fig. 7a,c,e, arrowheads) overlying the nodal axolemma as reported previously (Melendez-Vasquez et al, 2001). Colocalization of ezrin with ␤IV spectrin at the node (Fig.…”

Section: Rock Regulates the Organization Of Myelin Segments And Assocmentioning

confidence: 54%

“…Secondary antibodies conjugated to Rhodamine, fluorescein, coumarin, or cyanin 5 were obtained from Jackson Laboratories (West Grove, PA). Fixed samples (Schwann cells, myelinating coculture, frozen sections, and teased sciatic nerves) were permeabilized with acetone at Ϫ20°C, washed, and stained as described previously (Melendez-Vasquez et al, 2001). The tissue was examined by epifluorescence on a Zeiss (Thornwood, NY) Axiophot microscope and on a Zeiss LSM 510 confocal microscope.…”

Section: Methodsmentioning

confidence: 99%

“…Of interest, nodal axonal markers were exclusively localized in the gaps between MBPϩ segments even though redistribution of ERM proteins, a marker of Schwann cell processes that project to the node (Melendez-Vasquez et al, 2001), was incomplete. Recent studies suggest that contact-dependant signals, potentially involving interactions of the axon with ERMϩ processes, are important in node formation (Ching et al, 1999;MelendezVasquez et al, 2001;Gatto et al, 2003).…”

Section: Generation Of Axonal Domainsmentioning

confidence: 99%

“…The importance of the actin cytoskeleton was underscored by studies in which treatment of myelinating Schwann cell-neuron cocultures with cytochalasin D blocked ensheathment and myelination in a concentration-dependent manner (FernandezValle et al, 1997). Localization studies have demonstrated that actin and ERM (ezrin, radixin, and moesin) proteins, which are initially diffusely distributed, concentrate at either end of the Schwann cell just before myelination (Melendez-Vasquez et al, 2001;Pedraza et al, 2001) at tips of the cell that are dynamically active (Gatto et al, 2003). Actin microfilaments are also enriched in the processes of immature oligodendrocytes and, together with myosin IIB, are concentrated at the leading edges (Kachar et al, 1986;Wilson and Brophy, 1989;Song et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains

Melendez‐Vasquez

Einheber²,

Salzer³

2004

J. Neurosci.

107

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The myelin sheath forms by the spiral wrapping of a glial membrane around an axon. The mechanisms involved are poorly understood but are likely to involve coordinated changes in the glial cell cytoskeleton. Because of its key role as a regulator of the cytoskeleton, we investigated the role of Rho kinase (ROCK), a major downstream effector of Rho, in Schwann cell morphology, differentiation, and myelination. Pharmacologic inhibition of ROCK activity results in loss of microvilli and stress fibers in Schwann cell cultures and strikingly aberrant myelination in Schwann cell-neuron cocultures; there was no effect on Schwann cell proliferation or differentiation. Treated Schwann cells branch aberrantly and form multiple, small, independent myelin segments along the length of axons, each with associated nodes and paranodes. This organization partially resembles myelin formed by oligodendrocytes rather than the single long myelin sheath characteristic of Schwann cells. ROCK regulates myosin light chain phosphorylation, which is robustly, but transiently, activated at the onset of myelination. These results support a key role of Rho through its effector ROCK in coordinating the movement of the glial membrane around the axon at the onset of myelination via regulation of myosin phosphorylation and actomyosin assembly. They also indicate that the molecular machinery that promotes the wrapping of the glial membrane sheath around the axon is distributed along the entire length of the internode.

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Section: Rock Regulates the Organization Of Myelin Segments And Assocmentioning

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Section: Generation Of Axonal Domainsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains

Melendez‐Vasquez

Einheber²,

Salzer³

2004

J. Neurosci.

107

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“…), and the tissues were dissected and homogenized. For immunoprecipitation, solubilized proteins were precleared by protein A-agarose (Amersham Pharmacia) and incubated with 5 g of JN antibody or rabbit IgG (control) followed by 25 l of protein A-agarose (overnight at 4°C). Immunoprecipitated proteins were separated by SDS͞PAGE.…”

Section: Immunocytochemistry Electron Microscopy and Multiple Labelmentioning

confidence: 99%

Juxtanodin: An oligodendroglial protein that promotes cellular arborization and 2′,3′-cyclic nucleotide-3′-phosphodiesterase trafficking

Zhang

Cao²,

Guo³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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In the process of screening cell-type-specific genes, we identified juxtanodin (JN), an oligodendroglial protein featuring a putative C-terminal actin-binding domain. At the cellular level, JN in the rat CNS colocalized with 2 ,3 -cyclic nucleotide-3 -phosphodiesterase (CNPase), a cytoskeleton-related oligodendroglial protein. In the myelin sheath, JN was found mainly in the abaxon and the lateral few terminal loops. Its apposition to the myelinated axon, through the latter, defined an axonal subregion, herewith termed juxtanode, at the Ranvier node-paranode junction. During forebrain ontogenesis, JN expression paralleled that of MBPs but lagged behind CNPase. Juxtanodin transfection promoted arborization of cultured OLN-93 cells and augmented endogenous CNPase expression and transport to the process arbors of cultured primary oligodendrocyte precursors. These results reveal JN as a cytoskeleton-related oligodendroglial protein that delineates the juxtanode and might serve oligodendrocyte motility, differentiation, or myelin-axon signaling. Functionally, JN may be involved in CNS myelination and͞or specialization of the node of Ranvier.myelin-axon interaction ͉ oligodendrocyte ͉ node of Ranvier ͉ cytoskeleton O ligodendroglia are highly specialized myelin-forming cells of the CNS. Adequate myelination serves to insulate and accelerate the propagation of action potentials. Abnormalities in myelin formation͞maintenance may underlie diverse neurological disorders, ranging from multiple sclerosis to schizophrenia (1, 2). Matched with highly specialized functions and unique architecture, various oligodendrocyte͞myelin-selective molecules, such as myelin basic protein (MBP), myelin-associated glycoprotein, and 2Ј,3Ј-cyclic nucleotide-3Ј-phosphodiesterase (CNPase), have been isolated and characterized (1, 3). It is likely that many more are yet to be revealed. The identification and characterization of such molecules will probably help elucidate molecular mechanisms of myelination and dys-or demyelinating diseases.The unique architecture of the myelin sheath entails specialized, yet elusive, cytoskeletal mechanisms of myelin-forming cells. Here, we report the molecular features, cellular expression, and functional roles of juxtanodin (JN), a previously unidentified cytoskeleton-related oligodendrocyte-specific protein. Materials and MethodsIdentification and Characterization of the mRNA. Cell-type-specific CNS genes were sought out by in situ hybridization histochemistry (ISH). Briefly, cDNA clones (n ϭ 1,500) from a rat brain cDNA library (Invitrogen) were sequenced and compared by BLAST searches against National Center for Biotechnology Information nucleotide and protein nonredundant databases (4). For the unannotated cDNA sequences (n ϭ 274), expression of the mRNAs in the CNS was mapped by ISH using digoxigeninlabeled riboprobes. A 3.6-kb cDNA clone with a predicted ORF encoding 282 amino acid residues was thereby identified, and the gene was subsequently named juxtanodin (JN). A search of EST databases revealed an...

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Acute demyelination disrupts the molecular organization of peripheral nervous system nodes

Arroyo

Sirkowski

Chitale

et al. 2004

J of Comparative Neurology

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Intraneurally injected lysolecithin causes both segmental and paranodal demyelination. In demyelinated internodes, axonal components of nodes fragment and disappear, glial and axonal paranodal and juxtaparanodal proteins no longer cluster, and axonal Kv1.1/Kv1.2 K+ channels move from the juxtaparanodal region to appose the remaining heminodes. In paranodal demyelination, a gap separates two distinct heminodes, each of which contains the molecular components of normal nodes; paranodal and juxtaparanodal proteins are properly localized. As in normal nodes, widened nodal regions contain little or no band 4.1B. Lysolecithin also causes "unwinding" of paranodes: The spiral of Schwann cell membrane moves away from the paranodes, but the glial and axonal components of septate-like junctions remain colocalized. Thus, acute demyelination has distinct effects on the molecular organization of the nodal, paranodal, and juxtaparanodal region, reflecting altered axon-Schwann cell interactions.

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Nodes of Ranvier form in association with ezrin-radixin-moesin (ERM)-positive Schwann cell processes

Cited by 116 publications

References 36 publications

Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains

Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains

Juxtanodin: An oligodendroglial protein that promotes cellular arborization and 2′,3′-cyclic nucleotide-3′-phosphodiesterase trafficking

Acute demyelination disrupts the molecular organization of peripheral nervous system nodes

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