Critical and optimal Ig domains for promotion of neurite outgrowth by L1/Ng-CAM

Haspel, Jeffrey A.; Friedlander, David R.; Ivgy-May, Neely; Chickramane, Sucheta; Roonprapunt, Chan; Chen, Suzhen; Schachner, Melitta; Grumet, Martin

doi:10.1002/(sici)1097-4695(20000215)42:3<287::aid-neu1>3.3.co;2-o

Cited by 30 publications

(54 citation statements)

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“…The deduced full sequence of Losac indicates that the mature protein is made up of 395 amino acids resulting in a 43.4-kDa protein with a theoretical pI of 7.64 (JUFO program; available on the World Wide Web). Sequence Comparisons-Deduced amino acid sequence revealed variable percentages of identity with cell adhesion molecule members of the immunoglobulin superfamily: 26% identity with L1-NCAM (human neural cell adhesion molecule L1), which is involved in development of the nervous system and neurite outgrowth in humans (35); 34% identity with the four first domains of Neuroglian from Drosofila melanogaster (36), an ortholog of L1-NCAM; and between 47 and 76% identity with several members of the hemolin family (31). With the latter, rLosac shares the same multidomain structure (D1-D4, bars above sequences) and conserved motifs ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The analysis of the sequence revealed that Losac shares different degrees of similarity with cell adhesion molecule members of the immunoglobulin superfamily involved in the development of the nervous system and critical for neurite outgrowth: hemolin from lepidopters (47-76%) (31,37), neuroglian (34%) from D. melanogaster (36), and L1-NCAM (26%) from humans (35).…”

Section: Discussionmentioning

confidence: 99%

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Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation

Alvarez-Flores

Furlin

Ramos

et al. 2011

Journal of Biological Chemistry

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Envenoming by the contact of human skin with Lonomia obliqua caterpillars promotes a hemorrhagic syndrome characterized by a consumptive coagulopathy. Losac (Lonomia obliqua Stuart factor activator) is a component of the bristle of L. obliqua that is probably partially responsible for the observed syndrome because it activates factor X and is recognized by an effective antilonomic serum. Here we unveil the proteolytic activity of Losac and demonstrate the feasibility of its recombinant production. On the other hand, Losac has no homology to known proteases, but it can be inhibited by PMSF, a serine protease inhibitor. Instead, it shows closer homology to members of the hemolin family of proteins, a group of cell adhesion molecules. The recombinant protein (rLosac) shortened the coagulation time of normal and deficient plasmas, whereas it was ineffective in factor X-deficient plasma unless reconstituted with this protein. rLosac was able to activate factor X in a dose-and time-dependent manner but not ␥-carboxyglutamic acid domainless factor X. Moreover, phospholipids and calcium ions increased rLosac activity. Also, rLosac had no effect on fibrin or fibrinogen, indicating its specificity for blood coagulation activation. Linear double reciprocal plots indicate that rLosac follows a Michaelis-Menten kinetics. Cleavage of factor X by rLosac resulted in fragments that are compatible with those generated by RVV-X (a well known factor X activator). Together, our results validate Losac as the first protein from the hemolin family exhibiting procoagulant activity through selective proteolysis on coagulation factor X.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation

Alvarez-Flores

Furlin

Ramos

et al. 2011

Journal of Biological Chemistry

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“…The mouse CHL1-Fc and the mouse L1-Fc fusion proteins were produced and purified as described by Chen et al (1999) and Haspel et al (2000). They contain the extracellular domain of the mouse protein (CHL1 or L1) and the Fc region of the human IgG.…”

Section: Methodsmentioning

confidence: 99%

Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury

Jakovčevski

Wu²,

Karl³

et al. 2007

J. Neurosci.

113

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The Ig superfamily adhesion molecule CHL1, the close homolog of the adhesion molecule L1, promotes neurite outgrowth, neuronal migration, and survival in vitro. We tested whether CHL1, similar to its close homolog L1, has a beneficial impact on recovery from spinal cord injury using adult CHL1-deficient (CHL1 Ϫ/Ϫ ) mice and wild-type (CHL1 ϩ/ϩ ) littermates. In contrast to our hypothesis, we found that functional recovery, assessed by locomotor rating and video-based motion analyses, was improved in CHL1 Ϫ/Ϫ mice compared with wild-type mice at 3-6 weeks after compression of the thoracic spinal cord. Better function was associated with enhanced monoaminergic reinnervation of the lumbar spinal cord and altered pattern of posttraumatic synaptic rearrangements around motoneurons. Restricted recovery of wild-type mice was likely related to early and persistent (3-56 d after lesion) upregulation of CHL1 in GFAP-positive astrocytes at the lesion core. In both the intact spinal cord and cultured astrocytes, enhanced expression of CHL1 and GFAP was induced by application of basic fibroblast growth factor, a cytokine involved in the pathophysiology of spinal cord injury. This upregulation was abolished by inhibitors of FGF receptor-dependent extracellular signal-regulated kinase, calcium/calmodulin-dependent kinase, and phosphoinositide-3 kinase signaling pathways. In homogenotypic and heterogenotypic cocultures of neurons and astrocytes, reduced neurite outgrowth was observed only if CHL1 was simultaneously present on both cell types. These findings and novel in vitro evidence for a homophilic CHL1-CHL1 interaction indicate that CHL1 is a glial scar component that restricts posttraumatic axonal growth and remodeling of spinal circuits by homophilic binding mechanisms.

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“…Details on the production and characterisation of the monoclonal CEACAM1 antibody 4D1/C2 (in house preparation by Christoph Wagener (CW)) and the polyclonal L1 antibody (L1-S; in house preparation by Meliha Schachner (MS)) have been published previously (Haspel et al, 2000).…”

Section: Immuno-histochemistrymentioning

confidence: 99%

Clinically proven markers of metastasis predict metastatic spread of human melanoma cells engrafted in scid mice

et al. 2007

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Metastasis formation is a complex process and as such can only be modelled in vivo. As markers indicating metastatic spread in syngenic mouse models differ significantly from those in man, this study aimed to develop a human melanoma xenograft mouse model that reflects the clinical situation. Six human melanoma cell lines (LOX, MV3, FEMX-1, G361, MeWo and UISO-Mel6) were xenografted into severe combined immunodeficient mice and tumour growth, metastatic behaviour and number of lung metastases were assessed. Tumours and metastases were analysed for HPA binding and expression of CEACAM-1 and L1, all markers indicative of metastasis in clinical studies. Development of primary tumour nodules ranged from 3 weeks (MV3) to 3 months (MeWo). Whereas G361 and FEMX-1 rarely formed lung metastases, MeWo, MV3 and LOX were moderately and UISO-Mel6 was highly metastatic. Similar to clinical studies, HPA, CEACAM1 and L1 indicated metastatic spread in the xenograft melanoma model, but were not all simultaneously expressed in all cell lines. Considering the strongest expression of one marker combined with an absent or low expression of the other two markers, we conclude that LOX is the cell line of choice for analyses of the functional role of HPA-binding glycoconjugates, UISO-Mel6 is ideally suited to study CEACAM1 function in melanoma spread and L1 function can best be modelled using MeWo. Malignant melanoma, being the most aggressive form of skin cancer, represents a considerable clinical problem worldwide, where about 1 : 35 Caucasians will suffer from malignant melanoma during their lifetime with an incidence furthermore accelerating (Lens and Dawes, 2004). If the primary melanoma can be excised completely before it has spread to distant sites, the patient is cured. However, if metastases occur the patient's fate is sealed, as in spite of intensive research no curative treatment is yet available (Garbe and Blum, 2001;Eigentler et al, 2003). In order to make progress in the field of metastasis treatment, the process of malignant melanoma spread has to be better understood. Metastasis formation is a complex process, which involves many different steps, each of which has to be passed sequentially in order to lead to a clinically detectable metastasis (Hart and Saini, 1992). As this whole metastatic cascade is such a complex process, simple in vitro experiments can only partially mimick the course of metastatic spread and only animal experiments of metastasis can represent the full picture of this multistep phenomenon (Eccles, 2001).In melanoma metastasis research, the mouse B16 melanoma model has found widespread application (Tao et al, 1982). However, as this model represents a syngenic mouse model, it suffers the inherent problems of all murine models of metastasis, namely whether it is directly transferable to humans. Concerning carbohydrate expression, which has profound influence on the metastatic behaviour of tumour cells , murine B16 melanoma cells significantly differ from human melanoma cells. Expression of WGA and PHA...

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Critical and optimal Ig domains for promotion of neurite outgrowth by L1/Ng-CAM

Cited by 30 publications

References 0 publications

Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation

Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation

Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury

Clinically proven markers of metastasis predict metastatic spread of human melanoma cells engrafted in scid mice

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