Retention of a cell adhesion complex at the paranodal junction requires the cytoplasmic region of Caspr

Gollan, Leora; Sabanay, Helena; Poliak, Sebastian; Berglund, Erik; Ranscht, Barbara; Peles, Elior

doi:10.1083/jcb.200203050

Cited by 93 publications

(109 citation statements)

References 49 publications

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“…The Nf186 cDNA construct was a gift from Dr. Vann Bennett (Duke University, Durham, NC) (34). Nf155-Fc and Cn-Fc cDNA constructs were provided by Dr. Elior Peles (Weizmann Institute, Rehovot, Israel) (35,36). The Cn and Cn Ig -Fc constructs were gifts from Dr. Genviève Rougon (Laboratoire de Génétique et Physiologie du Dével-oppement, Marseille, France) (37).…”

Section: Methodsmentioning

confidence: 99%

“…The next morning, cells were washed with PBS and fixed with 4% paraformaldehyde. The cells were washed twice with PBS, followed by blocking with PBS containing 1% glycine and 10% goat serum (PBGG) for 30 min at room temperature as previously described (35). Primary antibodies were diluted in PBGG and incubated for 2 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…Binding and Immunofluorescence-Fc fusion protein binding assays were performed as previously described (35,36). 1610 Chinese hamster lung fibroblasts (CHL) (CRL-1657; American Type Culture Collection, Manassas, VA) grown in 8-well chamber slides (BD Biosciences) were transiently transfected with 0.5 g of a cDNA encoding a particular CAM, as indicated in the figure legends.…”

Section: Methodsmentioning

confidence: 99%

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Heterophilic Interactions of Sodium Channel β1 Subunits with Axonal and Glial Cell Adhesion Molecules

McEwen

Isom

2004

Journal of Biological Chemistry

103

101

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Voltage-gated sodium channels localize at high density in axon initial segments and nodes of Ranvier in myelinated axons. Sodium channels consist of a poreforming ␣ subunit and at least one ␤ subunit. ␤1 is a member of the immunoglobulin superfamily of cell adhesion molecules and interacts homophilically and heterophilically with contactin and Nf186. In this study, we characterized ␤1 interactions with contactin and Nf186 in greater detail and investigated interactions of ␤1 with NrCAM, Nf155, and sodium channel ␤2 and ␤3 subunits. Using Fc fusion proteins and immunocytochemical techniques, we show that ␤1 interacts with the fibronectin-like domains of contactin. ␤1 also interacts with NrCAM, Nf155, sodium channel ␤2, and Nf186 but not with sodium channel ␤3. The interaction of the extracellular domains of ␤1 and ␤2 requires the region 169 TEEEGKTDGEGNA 181 located in the intracellular domain of ␤2. Interaction of ␤1 with Nf186 results in increased Na v 1.2 cell surface density over ␣ alone, similar to that shown previously for contactin and ␤2. We propose that ␤1 is the critical communication link between sodium channels, nodal cell adhesion molecules, and ankyrin G .

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Heterophilic Interactions of Sodium Channel β1 Subunits with Axonal and Glial Cell Adhesion Molecules

McEwen

Isom

2004

Journal of Biological Chemistry

103

101

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“…NCP1 is the only identified AGJ axonal protein that contains a cytoplasmic domain. Evidence gathered from biochemical and transgenic mice studies showed that the cytoplasmic domain of NCP1 binds to the actin-spectrin binding protein 4.1B (27,28). There is growing realization that NCP1 mediates AGJ interactions with the axonal cytoskeleton and may participate in axon-glial signaling; however, physiological evidence to support these assumptions remains to be established.…”

mentioning

confidence: 97%

Disruption of axo–glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons

Garcia-Fresco

Sousa

Pillai

et al. 2006

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

121

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Axo-glial junctions (AGJs) play a critical role in the organization and maintenance of molecular domains in myelinated axons. Neurexin IV͞Caspr1͞paranodin (NCP1) is an important player in the formation of AGJs because it recruits a paranodal complex implicated in the tethering of glial proteins to the axonal membrane and cytoskeleton. Mice deficient in either the axonal protein NCP1 or the glial ceramide galactosyltransferase (CGT) display disruptions in AGJs and severe ataxia. In this article, we correlate these two phenotypes and show that both NCP1 and CGT mutants develop large swellings accompanied by cytoskeletal disorganization and degeneration in the axons of cerebellar Purkinje neurons. We also show that ␣II spectrin is part of the paranodal complex and that, although not properly targeted, this complex is still formed in CGT mutants. Together, these findings establish a physiologically relevant link between AGJs and axonal cytoskeleton and raise the possibility that some neurodegenerative disorders arise from disruption of the AGJs.myelin ͉ paranodes ͉ cerebellum ͉ ataxia T he anatomical organization of myelinated fibers into distinct domains is the basis for the saltatory mode of action potential propagation. In the axons, these molecular domains (internode, juxtaparanode, paranode, and node of Ranvier) form as a result of specific polarization driven by signaling between the myelinating glial cells and neurons that has yet to be fully understood. In the paranodal region, closely apposed axon-glial membranes form specialized cell junctions, which resemble the ladder-like invertebrate septate junctions, and are referred to as paranodal septate junctions or paranodal axo-glial junctions (AGJs) (1-4).Three major proteins have been shown to localize to the paranodal AGJs: NCP1 (also known as Caspr1 or paranodin) and contactin (CNTN) on the axonal side and neurofascin (NF155), the 155-kDa isoform on the glial side (5-9). Although NF155 is the only known glial protein at the paranodal membrane, a number of nonparanodal glial proteins are required for proper formation, maintenance, and distribution of AGJs, as in the case of ceramide galactosyltransferase (CGT), proteolipid protein, myelin-basic protein, myelin-associated glycoprotein, 2Ј,3Ј-cyclic nucleotide 3Ј-phosphodiesterase, and the transcription factor Nkx6-2 (10-17).Genetic ablation of NCP1 and CNTN in mice results in the loss of AGJs and a failure to segregate Na ϩ and K ϩ channels at the nodes and juxtaparanodes, respectively (5, 6). Similar phenotypes were observed at the paranodes in CGT mutants (18,19). CGT encodes an enzyme that is needed for the biosynthesis of two important myelin lipids, galactocerebroside and sulfatide (10,(18)(19)(20)(21). Using subcellular fractionation of NF155 in detergents, Rasband and coworkers (22) proposed a model in which myelin lipids assemble in stable lipid rafts to stabilize the clustering of NF155 at the glial side of AGJs. This model is consistent with the phenotype of CGT mutants in which defective biosynthes...

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“…Immunocytochemistry and immunohistochemistry were performed as described previously (Poliak et al, 2003). The following antibodies were used: mouse anti-GFAP (Sigma), rat anti-MBP (Chemicon, Temecula, CA), mouse anti-CNP (2Ј,3Ј-cyclic nucleotide 3Ј-phosphodiesterase) (Sigma), mouse anti-␤-tubulin IV (Sigma), rabbit anti-Caspr (Gollan et al, 2002), hybridoma supernatants of mouse antibodies to RIP, O4, Ran2, A2B5, and mouse anti-myelin oligodendrocyte glycoprotein (MOG) Z12 (generous gift from N. Schaeren-Wiemers, University Hospital Basel, Basel, Switzerland). Immunoelectron microscopy was performed as described previously (Gollan et al, 2002).…”

Section: Plasmids and Antibodiesmentioning

confidence: 99%

Ermin, A Myelinating Oligodendrocyte-Specific Protein That Regulates Cell Morphology

Brockschnieder¹,

Sabanay²,

Riethmacher³

et al. 2006

J. Neurosci.

106

102

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Oligodendrocytes form an insulating multilamellar structure of compact myelin around axons, thereby allowing rapid propagation of action potentials. Despite the considerable clinical importance of myelination, little is known about the molecular mechanisms that enable oligodendrocytes to generate their specialized membrane wrapping. Here, we used microarray expression profiling of oligodendrocyte-ablated mutant mice to identify new glial molecules that are involved in CNS myelination. This effort resulted in the identification of Ermin, a novel cytoskeletal molecule that is exclusively expressed by oligodendrocytes. Ermin appears at a late stage during myelination, and in the mature nerves, it is localized to the outer cytoplasmic lip of the myelin sheath and the paranodal loops. In cultured oligodendrocytes, Ermin becomes visible in well differentiated MBP-positive cells, where it is concentrated at the tip of F-actinrich processes (termed "Ermin spikes"). Ectopic expression of Ermin, but not of a mutant protein lacking its actin-binding domain, induced the formation of numerous cell protrusions and a pronounced change in cell morphology. Our results demonstrate that Ermin is a novel marker of myelinating oligodendroglia and suggest that it plays a role in cytoskeletal rearrangements during the late wrapping and/or compaction phases of myelinogenesis.

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Retention of a cell adhesion complex at the paranodal junction requires the cytoplasmic region of Caspr

Cited by 93 publications

References 49 publications

Heterophilic Interactions of Sodium Channel β1 Subunits with Axonal and Glial Cell Adhesion Molecules

Heterophilic Interactions of Sodium Channel β1 Subunits with Axonal and Glial Cell Adhesion Molecules

Disruption of axo–glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons

Ermin, A Myelinating Oligodendrocyte-Specific Protein That Regulates Cell Morphology

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