Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).

In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal.

Magnetotactic bacteria move by rotating their flagella and concomitantly are aligned to magnetic fields because they present magnetosomes, which are intracellular organelles composed by membrane-bound magnetic crystals. This results in magnetotaxis, which is swimming along magnetic field lines. Magnetotactic bacteria are morphologically diverse, including cocci, rods, spirilla and multicellular forms known as magnetotactic multicellular prokaryotes (MMPs). 'Candidatus Magnetoglobus multicellularis' is presently the best known MMP. Here we describe the helical trajectories performed by these microorganisms as they swim forward, as well as their response to UV light. We measured the radius of the trajectory, time period and translational velocity (velocity along the helix axis), which enabled the calculation of other trajectory parameters such as pitch, tangential velocity (velocity along the helix path), angular frequency, and theta angle (the angle between the helix path and the helix axis). The data revealed that 'Ca. M. multicellularis' swims along elongated helical trajectories with diameters approaching the diameter of the microorganism. In addition, we observed that 'Ca. M. multicellularis' responds to UV laser pulses by swimming backwards, returning to forward swimming several seconds after the UV laser pulse. UV light from a fluorescence microscope showed a similar effect. Thus, phototaxis is used in addition to magnetotaxis in this microorganism.

Magnetotactic bacteria orient and migrate along geomagnetic field lines. Each cell contains membrane-enclosed, nano-scale, iron-mineral particles called magnetosomes that cause alignment of the cell in the geomagnetic field as the bacteria swim propelled by flagella. In this work we studied the ultrastructure of the flagellar apparatus in many-celled magnetotactic prokaryotes (MMP) that consist of several Gram-negative cells arranged radially around an acellular compartment. Flagella covered the organism surface, and were observed exclusively at the portion of each cell that faced the environment. The flagella were helical tubes never as long as a complete turn of the helix. Flagellar filaments varied in length from 0.9 to 3.8 micro m (average 2.4 +/- 0.5 micro m, n = 150) and in width from 12.0 to 19.5 nm (average 15.9 +/- 1.4 nm, n = 52), which is different from previous reports for similar microorganisms. At the base of the flagella, a curved hook structure slightly thicker than the flagellar filaments was observed. In freeze-fractured samples, macromolecular complexes about 50 nm in diameter, which possibly corresponded to part of the flagella basal body, were observed in both the P-face of the cytoplasmic membrane and the E-face of the outer membrane. Transmission electron microscopy showed that magnetosomes occurred in planar groups in the cytoplasm close and parallel to the organism surface. A striated structure, which could be involved in maintaining magnetosomes fixed in the cell, was usually observed running along magnetosome chains. The coordinated movement of the MMP depends on the interaction between the flagella of each cell with the flagella of adjacent cells of the microorganism.