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

• DOI: 10.1038/cddis.2013.45
• Publication Date: 2013-03-21T15:24:28Z
• Authors: T C Izidoro-Toledo; A C Borges; D D Araújo; D P S Leitão Mazzi; F O Nascimento; J F Sousa; C P Alves; A P B Paiva; D M Trindade; E V Patussi; P M Peixoto; K W Kinnally; E M Espreafico
• Keywords: Cytoplasmic Dyneins; Mice, Knockout; 0303 health sciences; Bcl-2-Like Protein 11; Myosin Heavy Chains; Myosin Type V; Membrane Proteins; Apoptosis; DNA Fragmentation; Fibroblasts; Peptide Fragments; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Original Article; Apoptosis Regulatory Proteins; Melanoma; Neoplasm Transplantation; Adaptor Proteins, Signal Transducing; Protein Binding

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