Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis

Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies

Fine Tuning of Globin Gene Expression by DNA Methylation

Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. While the γ(A) and γ(G) genes are expressed in fetal liver, both are silenced in adult erythrocytes. In order to decipher the role of DNA methylation in this process, we generated a YAC transgenic mouse system that allowed us to control γ(A) methylation during development. DNA methylation causes a 20-fold repression of γ(A) both in non-erythroid and adult erythroid cells. In erythroid cells this modification works as a dominant mechanism to repress γ gene expression, probably through changes in histone acetylation that prevent the binding of erythroid transcription factors to the promoter. These studies demonstrate that DNA methylation serves as an elegant in vivo fine-tuning device for selecting appropriate genes in the globin locus. In addition, our findings provide a mechanism for understanding the high levels of γ-globin transcription seen in patients with Hereditary Persistence of Fetal Hemoglobin, and help explain why 5azaC and butyrate compounds stimulate γ-globin expression in patients with β-hemoglobinopathies

Planetary Rings

Planetary rings are the only nearby astrophysical disks, and the only disks that have been investigated by spacecraft. Although there are significant differences between rings and other disks, chiefly the large planet/ring mass ratio that greatly enhances the flatness of rings (aspect ratios as small as 1e-7), understanding of disks in general can be enhanced by understanding the dynamical processes observed at close-range and in real-time in planetary rings. We review the known ring systems of the four giant planets, as well as the prospects for ring systems yet to be discovered. We then review planetary rings by type. The main rings of Saturn comprise our system's only dense broad disk and host many phenomena of general application to disks including spiral waves, gap formation, self-gravity wakes, viscous overstability and normal modes, impact clouds, and orbital evolution of embedded moons. Dense narrow rings are the primary natural laboratory for understanding shepherding and self-stability. Narrow dusty rings, likely generated by embedded source bodies, are surprisingly found to sport azimuthally-confined arcs. Finally, every known ring system includes a substantial component of diffuse dusty rings. Planetary rings have shown themselves to be useful as detectors of planetary processes around them, including the planetary magnetic field and interplanetary impactors as well as the gravity of nearby perturbing moons. Experimental rings science has made great progress in recent decades, especially numerical simulations of self-gravity wakes and other processes but also laboratory investigations of coefficient of restitution and spectroscopic ground truth. The age of self-sustained ring systems is a matter of debate; formation scenarios are most plausible in the context of the early solar system, while signs of youthfulness indicate at least that rings have never been static phenomena.Comment: 82 pages, 34 figures. Final revision of general review to be published in "Planets, Stars and Stellar Systems", P. Kalas and L. French (eds.), Springer (http://refworks.springer.com/sss