Syndecan-3 and syndecan-4 are enriched in Schwann cell perinodal processes

BACKGROUND: Nodes of Ranvier correspond to specialized axonal domains where voltage-gated sodium channels are highly concentrated. In the peripheral nervous system, they are covered by Schwann cells microvilli, where three homologous cytoskeletal-associated proteins, ezrin, radixin and moesin (ERM proteins) have been found, to be enriched. These glial processes are thought to play a crucial role in organizing axonal nodal domains during development. However, little is known about the molecules present in Schwann cell processes that could mediate axoglial interactions. The aim of this study is to identify by immunocytochemistry transmembrane proteins enriched in Schwann cells processes that could interact, directly or indirectly, with axonal proteins. RESULTS: We show that syndecan-3 (S3) and syndecan-4 (S4), two proteoglycans expressed in Schwann cells, are enriched in perinodal processes in rat sciatic nerves. S3 labeling was localized in close vicinity of sodium channels as early as post-natal day 2, and highly concentrated at nodes of Ranvier in the adult. S4 immunoreactivity accumulated at nodes later, and was also prominent in internodal regions of myelinated fibers. Both S3 and S4 were co-localized with ezrin in perinodal processes. CONCLUSIONS: Our data identify S3 and S4 as transmembrane proteins specifically enriched in Schwann cell perinodal processes, and suggest that S3 may be involved in early axoglial interactions during development

Entrepreneurial tendencies among highly educated students in Germany and Italy - A cross-national study

Continuous and breakthrough industrial innovations are essential for sustainability and the success of modern economies. As the development of innovative products and technologies is often performed within start-up enterprises, the facilitation of entrepreneurial spirit is of major political interest. However, central European countries like Italy and Germany lack behind as highly educated students rather prefer more conventional career paths. In this study we surveyed Bachelor, Master and PhD students in Germany and Italy to further understand the cultural and socio-geographic effects on career decisions. Although only minor differences could be detected among the peer-group, beneficial observations were derived, identifying key-motivators and cultural necessities

Selective Axonal Expression of the Kv1 Channel Complex in Pre-myelinated GABAergic Hippocampal Neurons.

In myelinated fibers, the voltage-gated sodium channels Nav1 are concentrated at the nodal gap to ensure the saltatory propagation of action potentials. The voltage-gated potassium channels Kv1 are segregated at the juxtaparanodes under the compact myelin sheath and may stabilize axonal conduction. It has been recently reported that hippocampal GABAergic neurons display high density of Nav1 channels remarkably in clusters along the axon before myelination (Freeman et al., 2015). In inhibitory neurons, the Nav1 channels are trapped by the ankyrinG scaffold at the axon initial segment (AIS) as observed in pyramidal and granule neurons, but are also forming "pre-nodes," which may accelerate conduction velocity in pre-myelinated axons. However, the distribution of the Kv1 channels along the pre-myelinated inhibitory axons is still unknown. In the present study, we show that two subtypes of hippocampal GABAergic neurons, namely the somatostatin and parvalbumin positive cells, display a selective high expression of Kv1 channels at the AIS and all along the unmyelinated axons. These inhibitory axons are also highly enriched in molecules belonging to the juxtaparanodal Kv1 complex, including the cell adhesion molecules (CAMs) TAG-1, Caspr2, and ADAM22 and the scaffolding protein 4.1B. Here, taking advantage of hippocampal cultures from 4.1B and TAG-1 knock-out mice, we observed that 4.1B is required for the proper positioning of Caspr2 and TAG-1 along the distal axon, and that TAG-1 deficiency induces alterations in the axonal distribution of Caspr2. However, the axonal expression of Kv1 channels and clustering of ankyrinG were not modified. In conclusion, this study allowed the analysis of the hierarchy between channels, CAMs and scaffolding proteins for their expression along hippocampal inhibitory axons before myelination. The early steps of channel compartmentalization preceding myelination may be crucial for stabilizing nerve impulses switching from a continuous to saltatory conduction during network development

Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers

Myelination results in a highly segregated distribution of axonal membrane proteins at nodes of Ranvier. Here, we show the role in this process of TAG-1, a glycosyl-phosphatidyl-inositol–anchored cell adhesion molecule. In the absence of TAG-1, axonal Caspr2 did not accumulate at juxtaparanodes, and the normal enrichment of shaker-type K+ channels in these regions was severely disrupted, in the central and peripheral nervous systems. In contrast, the localization of protein 4.1B, an axoplasmic partner of Caspr2, was only moderately altered. TAG-1, which is expressed in both neurons and glia, was able to associate in cis with Caspr2 and in trans with itself. Thus, a tripartite intercellular protein complex, comprised of these two proteins, appears critical for axo–glial contacts at juxtaparanodes. This complex is analogous to that described previously at paranodes, suggesting that similar molecules are crucial for different types of axo–glial interactions

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber

Rôle de SCHIP-1 dans l'organisation et la fonction des fibres myélinisées

Les noeuds de Ranvier (NR) et les segments initiaux (SI) sont responsables de la génération et de la propagation rapide des potentiels d action le long de la fibre myélinisée, respectivement. Des canaux Na+ dépendants du voltage sont concentrés dans ces deux régions où ils font partie de complexes multimoléculaires incluant notamment les protéines du cytosquelette ankyrine G et spectrine bIV. Nos travaux décrivent l identification d un nouveau composant enrichi à la membrane axonale de ces deux régions : SCHIP-1. L ankyrine G et spectrine bIV sont toutes deux indispensables à la localisation de SCHIP-1 aux SI et/ou aux NR et la région C-terminale de SCHIP-1 est capable d interagir avec l ankyrine G. Nous avons produit des souris mutantes exprimant une forme tronquée de SCHIP-1, délétée de sa partie C-terminale. L étude de ces souris montre que la délétion de SCHIP-1 perturbe l organisation de la fibre myélinisée comme l indiquent notamment les anomalies de la morphologie et du nombre des NR et la diminution du nombre de fibres dans les nerfs périphériques. Les retentissements de la délétion de SCHIP-1 sur le phénotype des souris sont multiples. Les souris 10/ 10 accusent un léger retard de croissance et souffrent d une mauvaise coordination des mouvements. D autre part les souris SCHIP-1 10/ 10 ont des déficits importants d interactions sociales et montrent des comportements stéréotypés, deux des trois symptômes majeurs de l autisme, une observation à mettre en rapport avec le rôle possible de SCHIP-1 dans les troubles de type autisme chez l'humain.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF