Caspr regulates the processing of contactin and inhibits its binding to neurofascin

Gollan, Leora; Salomon, Daniela; Salzer, James L.; Peles, Elior

doi:10.1083/jcb.200309147

Cited by 129 publications

(144 citation statements)

References 24 publications

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“…These results are similar to the interaction previ- ously described for contactin with Nf155 and confirmed in Fig. 2C (36). In contrast, a Fc fusion construct consisting only of the six Ig domains of contactin and not the fibronectin-like domains, Cn Ig -Fc, did not bind ␤1 (Fig.…”

Section: ␤1 Interacts With the Fibronectin-like Domains Of Contactin-supporting

confidence: 90%

“…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%

“…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%

“…1A) (18,36,37,44) as well as full-length Nf186, full-length ␤2, and the truncation mutant ␤2 STOP (22,34). Immunoblots of cell supernatants from transiently transfected CHL fibroblasts indicated expression of all of the soluble Fc fusion proteins used (Fig.…”

Section: Production Of Fc Fusion Proteins and Binding Assays-tomentioning

confidence: 96%

“…Axo-glial septate-like junctions are formed through interactions between contactin and Caspr on the axonal membrane (6 -8, 33). Nf155 may be the glial receptor for the contactin-Caspr complex, although recent evidence has shown that Caspr may negatively regulate interactions between contactin and Nf155 (36). Our next step was to test for ␤1 interactions with Nf155.…”

Section: ␤1 Interacts With the Fibronectin-like Domains Of Contactin-mentioning

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: ␤1 Interacts With the Fibronectin-like Domains Of Contactin-supporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Production Of Fc Fusion Proteins and Binding Assays-tomentioning

confidence: 96%

Section: ␤1 Interacts With the Fibronectin-like Domains Of Contactin-mentioning

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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Phase II study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in patients with taxane‐refractory/resistant nonsmall cell lung carcinoma

Kim

Kies

Fossella

et al. 2005

Cancer

105

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BACKGROUNDThe authors evaluated the safety, tolerability, and efficacy of treatment using lonafarnib, a novel farnesyltransferase inhibitor (FTI), in combination with paclitaxel in patients with metastatic (Stage IIIB/V), taxane‐refractory/resistant nonsmall cell lung carcinoma (NSCLC).METHODSPatients with NSCLC who experienced disease progression while receiving previous taxane therapy or who had disease recurrence within 3 months after taxane therapy cessation were treated with continuous lonafarnib 100 mg orally twice per day beginning on Day 1 and paclitaxel 175 mg/m2 intravenously over 3 hours on Day 8 of each 21‐day cycle.RESULTSA total of 33 patients were enrolled, 29 of whom were evaluable for response. Partial responses (PR) and stable disease (SD) were observed in 3 (10%) and 11 patients (38%), respectively. Thus, 48% (14 of 29) experienced clinical benefit (PR or SD). The updated and final median overall survival time was 39 weeks and the median disease progression‐free survival time was 16 weeks. The combination of lonafarnib and paclitaxel was well tolerated with minimal toxicity. Grade 3 toxicities included fatigue (9%), diarrhea (6%), and dyspnea (6%). Grade 3 neutropenia occurred in only 1 patient (3%). Grade 4 adverse events included respiratory insufficiency in 2 patients (6%) and acute respiratory failure in 1 patient (3%).CONCLUSIONSLonafarnib plus paclitaxel demonstrated clinical activity in patients with taxane‐refractory/resistant metastatic NSCLC. In addition, the combination of lonafarnib and paclitaxel was well tolerated with minimal toxicity. Evaluation of this combination therapy in additional clinical trials is warranted. Cancer 2005. © 2005 American Cancer Society.

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Age‐related molecular reorganization at the node of Ranvier

Hinman

Peters

Cabral

et al. 2006

J of Comparative Neurology

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In myelinated axons, action potential conduction is dependent on the discrete clustering of ion channels at specialized regions of the axon, termed nodes of Ranvier. This organization is controlled, at least in part, by the adherence of myelin sheaths to the axolemma in the adjacent region of the paranode. Age-related disruption in the integrity of internodal myelin sheaths is welldescribed and includes splitting of myelin sheaths, redundant myelin, and fluctuations in biochemical constituents of myelin. These changes have been proposed to contribute to agerelated cognitive decline since in previous studies of monkeys, myelin changes correlate with cognitive performance. In the present study, we hypothesize that age-dependent myelin breakdown results in concomitant disruption at sites of axoglial contact, in particular at the paranode and that this disruption alters the molecular organization in this region. In aged monkey and rat optic nerves, immunolabeling for voltage-dependent potassium channels of the Shaker family (Kv1.2), normally localizing in the adjacent juxtaparanode, were mislocalized to the paranode. Similarly, immunolabeling for the paranodal marker, caspr, reveals irregular casprlabeled paranodal profiles, suggesting there may be age-related changes in paranodal structure. Ultrastructural analysis of paranodal segments from optic nerve of aged monkeys shows that in a subset of myelinated axons with thick sheaths, some paranodal loops fail to contact the axolemma. Thus, age-dependent myelin alterations affect axonal protein localization and may be detrimental to maintenance of axonal conduction.

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Caspr regulates the processing of contactin and inhibits its binding to neurofascin

Cited by 129 publications

References 24 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

Phase II study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in patients with taxane‐refractory/resistant nonsmall cell lung carcinoma

Age‐related molecular reorganization at the node of Ranvier

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