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

Effet d’une situation d’apnée statique sur les capacités individuelles d’estimation du temps

International audienceIntroduction. – Apnea is known to induce specific physiological adaptation in order to protect brain and heart from hypoxia. During apnea, ability to accurately estimate time is the main factor to keep watch over it in order to perform safely. Therefore, the present study aimed to analyse the effect of static apnea on internal clock processes.Fact synthesis. – As expected, continuous heart rate monitoring appeared to be a good marker of biological activity. Five trials of time production (20 s) were performed by the subjects, in a sitting position using a chronometer. Time production was studied during three experimental conditions: at rest before static apnea, during five short static apneas (less than 1 min) and at rest after static apneas. Compared to rest, static apnea induced a bradycardia and an underestimation of time interval.Conclusion. – As previously reported in the literature, time processes and biological activity seemed to be connected. The apneic bradycardia could reflect a decrease in biological activity (primarily in order to decrease oxygen uptake) which might consequently influence time estimation mechanisms. If subjects underestimate time during static apnea, then any additional time spent in breath-hold condition could increase oxygen deficit and therefore lead to free diving accident.Introduction. – L'apnée réalisée en milieu aérien comme aquatique induit des adaptations physiologiques ayant pour objectif de maintenir la perfusion des organes « nobles » (cerveau, coeur). Lors de sa réalisation en immersion, la gestion du temps est primordiale afin d'accomplir une performance sans se mettre en situation de danger. Ainsi, on peut se demander dans quelles mesures l'apnée statique peut perturber l'estimation du temps ?Synthèse des faits. – La fréquence cardiaque des sujets, enregistrée en continu, peut être considérée comme un bon témoin du niveau de l'activité biologique. Les productions des sujets (production manuelle avec un chronomètre d'un intervalle estimé de 20 s) en situation de repos (position assise) et de récupération ne sont pas significativement différentes et sont considérées comme valeurs contrôles. L'apnée statique, qui induit une bradycardie, est également accompagnée d'une sous-estimation de la durée écoulée, mais significativement plus importante que lors du repos.Conclusion. – Il semble exister une corrélation entre le niveau d'activité biologique et les processus d'estimation temporelle : la bradycardie apnéique semble être le reflet d'une baisse de l'activité biologique entraînant une mauvaise estimation de la durée écoulée. Les sujets sous-estiment le temps en apnée statique, augmentant ainsi les déficits en oxygène de l'organisme et par conséquent le facteur de risque de syncopes hypoxiques

Protooncogene Ski cooperates with the chromatin-remodeling factor Satb2 in specifying callosal neurons

First insights into the molecular programs orchestrating the progression from neural stem cells to cortical projection neurons are emerging. Loss of the transcriptional regulator Ski has been linked to the human 1p36 deletion syndrome, which includes central nervous system defects. Here, we report critical roles for Ski in the maintenance of the neural stem cell pool and the specification of callosal neurons. Ski-deficient callosal neurons lose their identity and ectopically express the transcription factor Ctip2. The misspecified callosal neurons largely fail to form the corpus callosum and instead redirect their axons toward subcortical targets. We identify the chromatin-remodeling factor Satb2 as a partner of Ski, and show that both proteins are required for transcriptional repression of Ctip2 in callosal neurons. We propose a model in which Satb2 recruits Ski to the Ctip2 locus, and Ski attracts histone deacetylases, thereby enabling the formation of a functional nucleosome remodeling and deacetylase repressor complex. Our findings establish a central role for Ski–Satb2 interactions in regulating transcriptional mechanisms of callosal neuron specification