Modulation of Extracellular Matrix Adhesiveness by Neurocan and Identification of Its Molecular Basis

Talts, Ulrika; Kuhn, Ursula; Roos, G; Rauch, Uwe

doi:10.1006/excr.2000.4987

Cited by 20 publications

(22 citation statements)

References 47 publications

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“…Construction of recombinant full-length neurocan and the neurocan fragment D925, L639, and 773M, respectively, has been described previously (22). The production and characterization of all other neurocan fragments are described in full detail in a separate paper (23). In fragments D925⌬S and D925⌬T a stop codon was introduced after threonine 1153 and after arginine 1216, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Purified neurocan and subfragments were analyzed by SDS-PAGE and Western blot analysis as described previously (22,23).…”

Section: Methodsmentioning

confidence: 99%

“…5). Both truncated molecules were modified with chondroitin sulfate chains and secreted in similar amounts by transfected HEK 293 EBNA cells (23). The NC⌬L construct was deficient for the second EGF module and the C-type lectin module but contained the sushi module and the appending tail (Fig.…”

Section: The First Ig Domain Is the Only Neurocan-binding Site In L1-mentioning

confidence: 99%

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Characterization of the L1-Neurocan-binding Site

Oleszewski

Gutwein

Lieth

et al. 2000

Journal of Biological Chemistry

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The L1 adhesion molecule is a 200 -220-kDa membrane glycoprotein of the Ig superfamily implicated in important neural processes including neuronal cell migration, axon outgrowth, learning, and memory formation. L1 supports homophilic L1-L1 binding that involves several Ig domains but can also bind with high affinity to the proteoglycan neurocan. It has been reported that neurocan can block homophilic binding; however, the mechanism of inhibition and the precise binding sites in both molecules have not been determined. By using fusion proteins, site-directed mutagenesis, and peptide blocking experiments, we have characterized the neurocanbinding site in the first Ig-like domain of human L1. Results from molecular modeling suggest that the sequences involved in neurocan binding are localized on the surface of the first Ig domain and largely overlap with the G-F-C ␤-strands proposed to interact with the fourth Ig domain during homophilic binding. This suggests that neurocan may sterically hinder a proper alignment of L1 domains. We find that the C-terminal portion of neurocan is sufficient to mediate binding to the first Ig domain of L1, and we suggest that the sushi domain cooperates with a glycosaminoglycan side chain in forming the binding site for L1.

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Section: Methodsmentioning

confidence: 99%

“…Purified neurocan and subfragments were analyzed by SDS-PAGE and Western blot analysis as described previously (22,23).…”

Section: Methodsmentioning

confidence: 99%

Section: The First Ig Domain Is the Only Neurocan-binding Site In L1-mentioning

confidence: 99%

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Characterization of the L1-Neurocan-binding Site

Oleszewski

Gutwein

Lieth

et al. 2000

Journal of Biological Chemistry

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“…The transfected rat neurocan and rat brevican cDNAs had been modified by changing the endogenous 5Ј untranslated sequences and the signal peptide against the corresponding sequences of BM40 as described (Feng et al, 2000;Talts et al, 2000). CSPG content of the supernatants was verified by SDS-PAGE and staining with Coomassie Blue (supplementary material Fig.…”

Section: Proteins and Antibodiesmentioning

confidence: 99%

Competition and cooperation between tenascin-R, lecticans and contactin 1 regulate neurite growth and morphology

Zacharias

Rauch

2006

Journal of Cell Science

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The extracellular matrix molecule tenascin-R (TN-R) and the proteoglycans of the lectican family show an overlapping distribution in the developing brain, have been implicated in similar cellular processes and form a complex network of interactions. Previously, we have demonstrated that TN-R induces microprocesses along neurites and enlarged growth cones of tectal cells by interacting with the cell adhesion molecule contactin 1. Here, we describe competition and cooperation between TN-R, lecticans and contactin 1, and their functional consequences for tectal cells. Aggrecan, brevican and neurocan inhibit the effects of TN-R on microprocess formation and growth cone size. This blocking effect is due to competition of lecticans with binding of TN-R to its neuronal receptor contactin 1, as shown by a sandwich-binding assay. Interaction of aggrecan with TN-R fibronectin type III domains 4-A is necessary for its inhibitory effect on both microprocess formation and TN-R binding to contactin 1. However, the chondroitin sulfate chains are not involved. Time-lapse video microscopy showed that aggrecan has no acute effect on motility and morphology of microprocesses and growth cones but induces long-term neurite retraction after pre-treatment with TN-R. In contrast to the competition described above, TN-R cooperates with brevican and neurocan to induce attachment of tectal cells and neurite outgrowth, probably by forming a bridge between the lectican substrate and contactin 1 as the neuronal receptor. Our findings suggest that a complex network of protein-protein interactions within the brain extracellular matrix, as shown here for TN-R and lecticans, is important for the fine-regulation of developmental processes such as microprocess formation along the neurite and neurite outgrowth.

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“…The interaction of neurocan with GalNAcPTase involves the N-terminal portion of the molecule (Li et al, 2000). The C-terminal portion of the molecule has also been found to have an anti-adhesive activity (Talts et al, 2000).…”

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confidence: 99%

Neurocan in the embryonic avian heart and vasculature

Mishima

Hoffman

2003

Anat. Rec.

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The chondroitin sulfate proteoglycan (CSPG) neurocan was previously considered to be nervous-system specific. However, we have found neurocan in the embryonic heart and vasculature. In stage 11 quail embryos, neurocan was prominently expressed in the myocardium, dorsal mesocardium, heart-forming fields, splanchnic mesoderm, and vicinity of the extraembryonic vaculature, and at lower levels in the endocardium. A comparison of neurocan staining with QH1 staining of vascular endothelial cells demonstrates that neurocan is frequently expressed by cells adjacent to endothelial cells, rather than by endothelial cells themselves. In some cases, a dispersed subset of cells are neurocan-positive in a field of cells that otherwise appear uniform in morphology. Later in development, neurocan expression becomes relatively limited to the nervous system. However, even in 10-day embryos, neurocan is expressed in the chorio-allantoic membrane in the tissue that separates closely packed, small-diameter blood vessels. In summary, our results suggest that neurocan may function as a barrier that regulates vascular patterning during development. Anat Rec Part A 272A: 556 -562, 2003.

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Modulation of Extracellular Matrix Adhesiveness by Neurocan and Identification of Its Molecular Basis

Cited by 20 publications

References 47 publications

Characterization of the L1-Neurocan-binding Site

Characterization of the L1-Neurocan-binding Site

Competition and cooperation between tenascin-R, lecticans and contactin 1 regulate neurite growth and morphology

Neurocan in the embryonic avian heart and vasculature

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