Biomedical subjects

Marc Niere

Publications and source records attributed to Marc Niere.

5 recordsLinked to original sources

PubMed2006

Combination of engineered neural cell adhesion molecules and GDF-5 for improved neurite extension in nerve guide concepts.

Current therapeutical approaches for the treatment of severe lesions in the peripheral nervous system rely on the use of autologous tissue or the body's own Schwann cells. However, these approaches are limited and alternative strategies for peripheral nerve regeneration are required. Here we evaluate combinations of a variety of neuronal regeneration factors including engineered cell adhesion molecules and growth factors in embryonic model neurons to test the possible improvement of artificial nerve guides by cooperative mechanisms. Cell adhesion molecules L1 and neurofascin synergistically promote neurite elongation. The outgrowth promoting properties of both proteins can be combined and further increased within one chimeric protein. Addition of growth and differentiation factor 5 (GDF-5) further enhances neurite outgrowth in a substrate-independent manner. This effect is not due to a protective mode of action of GDF-5 against pro-apoptotic stimuli. Consequently, the study supports the idea that different modes of action of pro-regenerative factors may contribute synergistically to neurite outgrowth and emphasizes the applicability of combinations of proteins specifically involved in development of the nervous system for therapeutical approaches.

Animals↗

PubMed2005

A regulated switch of chick neurofascin isoforms modulates ligand recognition and neurite extension.

Neural cell adhesion molecule neurofascin regulates the induction of neurite outgrowth, the establishment of synaptic connectivity and myelination. Neurofascin isoforms are generated by spatially and temporally controlled alternative splicing. Isoform NF166 is predominantly expressed in dorsal root ganglia from embryonal day 5 (E5) to E8, and a further neurofascin isoform NF185 appears at E9. Expression of neurofascin and its binding partner axonin-1 on sensory fibers implies functional interactions for neurite outgrowth. E7 sensory neurons require NF166-axonin-1 interactions for neurite extension, accordingly. The contribution of NF166-axonin-1 interaction for neurite outgrowth decreases in parallel with the appearance of NF185 on sensory neurons at E9. This finding may be explained by (1) alleviated intrinsic capability to use axonin-1 as a cellular receptor and (2) reduced binding of axonin-1 to NF185. Finally, NF166, but not NF185, serves as a cellular receptor for neurite induction via homophilic interactions with a neurofascin substrate.

Alternative Splicing↗

PubMed2004

NAD+ surfaces again.

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Adenosine Diphosphate Ribose↗

PubMed2004

Homophilic interactions of chick neurofascin in trans are important for neurite induction.

Neurofascin is a member of the immunoglobulin superfamily involved in axon extension and fasciculation. Here we apply adenoviral short hairpin RNA (shRNA) expression in primary neurons, PC12-NIH/3T3 co-cultures in combination with Luminex assays, to demonstrate homophilic interactions of neurofascin for neurite outgrowth. An adenoviral vector was constructed for the expression of shRNA in primary tectal cells that inhibits gene expression similar to short interfering RNA. We demonstrate that after shRNA-mediated knockdown neuronal neurofascin expression is important for neurite outgrowth on a neurofascin substrate. Neurite outgrowth assays reveal that neurite formation of PC12 cells is increased when neurofascin is overexpressed on both outgrowing PC12 cells and substrate NIH/3T3 cells, suggesting that neurofascin expression is also sufficient for neurite induction. Luminex technology for the analysis of protein-protein interactions showed homophilic binding of neurofascin to itself.

Adenoviridae↗

PubMed2002

Differential lipid binding of truncation mutants of Galleria mellonella apolipophorin III.

Apolipophorin III (apoLp-III) is a prototype exchangeable apolipoprotein that is amenable to structure-function studies. The protein folds as a bundle of five amphipathic alpha-helices and undergoes a dramatic conformational change upon lipid binding. Recently, we have shown that a truncation mutant of Galleria mellonella apoLp-III comprising helices 1-3 is stable in solution and able to bind to lipid surfaces [Dettloff, M., Weers, P. M. M., Niere, M., Kay, C. M., Ryan, R. O., and Wiesner, A. (2001) Biochemistry 40, 3150-3157]. To investigate the role of the C-terminal helices in apoLp-III structure and function, two additional 3-helix mutants were designed: a core fragment comprising helix (H) 2-4, and a C-terminal fragment (H3-5). Each truncation mutant retained the ability to associate spontaneously with dimyristoylphosphatidylcholine (DMPC) vesicles, transforming them into discoidal complexes. The rate of apolipoprotein-dependent DMPC vesicle transformation decreased in the order H1-3 > H2-4 > H3-5. Truncation of two helices led to a significant decrease in alpha-helical content in buffer in each case, from 86% (wild-type) to 50% (H1-3), 28% (H2-4), and 24% alpha-helical content (H3-5). On the other hand, trifluoroethanol or complexation with DMPC induced the truncation mutants to adopt a high alpha-helical structure similar to that of wild-type protein (84-100% alpha-helical structure). ApoLp-III(H1-3) and apoLp-III(H2-4), but not apoLp-III(H3-5), were able to prevent phospholipase-C-induced low density lipoprotein aggregation, indicating that interaction of the C-terminal fragment with spherical lipoprotein surfaces was impaired. As lipoprotein binding is significantly affected and DMPC transformation rates are relatively slow upon removal of N-terminal helices, the data indicate that structural elements necessary for lipid interaction reside in the N-terminal part of the protein.

Animals↗