The GTPase dynamin polymerizes into a helical coat that constricts membrane necks of endocytic pits to promote their fission. However, the dynamin mechanism is still debated because constriction is necessary but not sufficient for fission. Here, we show that fission occurs at the interface between the dynamin coat and the uncoated membrane. At this location, the considerable change in membrane curvature increases the local membrane elastic energy, reducing the energy barrier for fission. Fission kinetics depends on tension, bending rigidity, and the dynamin constriction torque. Indeed, we experimentally find that the fission rate depends on membrane tension in vitro and during endocytosis in vivo. By estimating the energy barrier from the increased elastic energy at the edge of dynamin and measuring the dynamin torque, we show that the mechanical energy spent on dynamin constriction can reduce the energy barrier for fission sufficiently to promote spontaneous fission. :

Dynamin, which mediates membrane fission during endocytosis, binds endophilin and other members of the Bin-Amphiphysin-Rvs (BAR) protein family. How endophilin influences endocytic membrane fission is still unclear. Here, we show that dynamin-mediated membrane fission is potently inhibited in vitro when an excess of endophilin co-assembles with dynamin around membrane tubules. We further show by electron microscopy that endophilin intercalates between turns of the dynamin helix and impairs fission by preventing trans interactions between dynamin rungs that are thought to play critical roles in membrane constriction. In living cells, overexpression of endophilin delayed both fission and transferrin uptake. Together, our observations suggest that while endophilin helps shape endocytic tubules and recruit dynamin to endocytic sites, it can also block membrane fission when present in excess by inhibiting inter-dynamin interactions. The sequence of recruitment and the relative stoichiometry of the two proteins may be critical to regulated endocytic fission.

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Centronuclear myopathies (CNMs) are genetic diseases whose symptoms are muscle weakness and atrophy (wasting) and centralised nuclei. Recent human genetic studies have isolated several groups of mutations. Among them, many are found in two interacting proteins essential to clathrin-mediated endocytosis, dynamin and the BIN-Amphiphysin-Rvs (BAR) protein BIN1/amphiphysin 2. In this review, by using structural and functional data from the study of endocytosis mainly, we discuss how the CNM mutations could affect the structure and the function of these ubiquitous proteins and cause the muscle-specific phenotype. The literature shows that both proteins are involved in the plasma membrane tubulation required for T-tubule biogenesis. However, this system also requires the regulation of the dynamin-mediated membrane fission, and the formation of a stable protein-scaffold to maintain the T-tubule structure. We discuss how the specific functions, isoforms and partners (myotubularin in particular) of these two proteins can lead to the establishment of muscle-specific features.

Patients seeking bariatric surgery showed different psychopathological features compared with those seeking a non-surgical approach. This suggests the importance for clinicians to consider that patients could seek bariatric surgery on the basis of the severity of the psychological distress associated with their morbid obesity, rather than criteria only based on clinical indication.