A myosin-Va tail fragment sequesters dynein light chains leading to apoptosis in melanoma cells

Previous studies proposed that myosin-Va regulates apoptosis by sequestering pro-apoptotic Bmf to the actin cytoskeleton through dynein light chain-2 (DLC2). Adhesion loss or other cytoskeletal perturbations would unleash Bmf, allowing it to bind and inhibit pro-survival Bcl2 proteins. Here, we demonstrated that over expression of a myosin-Va medial tail fragment (MVaf) harboring the binding site for DLC2 dramatically decreased melanoma cell viability. Morphological and molecular changes, including surface blebbing, mitochondrial outer membrane permeabilization, cytochrome-c and Smac release, as well as caspase-9/-3 activation and DNA fragmentation indicated that melanoma cells died of apoptosis. Immobilized MVaf interacted directly with DLCs, but complexed MVaf/DLCs did not interact with Bmf. Overexpression of DLC2 attenuated MVaf-induced apoptosis. Thus, we suggest that, MVaf induces apoptosis by sequestering DLC2 and DLC1, thereby unleashing the pair of sensitizer and activator BH3-only proteins Bmf and Bim. Murine embryonic fibroblasts (MEFs) lacking Bim and Bmf or Bax and Bak were less sensitive to apoptosis caused by MVaf expression than wild-type MEFs, strengthening the putative role of the intrinsic apoptotic pathway in this response. Finally, MVaf expression attenuated B16-F10 solid tumor growth in mice, suggesting that this peptide may be useful as an apoptosis-inducing tool for basic and translational studies

Socio-environmental conditions of Minas Gerais migrants in Piracicaba, SP, Brazil

Migration is one of the most important strategies of survival mankind. It has allowed man to occupy new environments and find better living conditions than the original ones. A previous report identified in Piracicaba, State of Sao Paulo, Brazil, a large contingent of migrants originating at the Municipality of Novo Cruzeiro, State of Minas Gerais. The present study explores whether migrant families from Cruzeiro to Piracicaba have now reached similar or better living conditions as those of the inhabitants of the former location, justifying the their moving. Evidence has shown that migrant families from Novo Cruzeiro to Piracicaba have reached similar or better living conditions than those families who remained home (Novo Cruzeiro-MG), which justify moving from one state to another Socio-environmental indicators showed that living conditions improved among the Piracicaba inhabitants as to housing, family income and maternal school attendance.30955555