title: Programming membrane fusion and subsequent apoptosis into mammalian cells.
abstract: By the delivery of specific natural or engineered proteins, mammalian cells can be programmed to perform increasingly sophisticated and useful functions. Here, we introduce a set of proteins that has potential value in cell-based therapies by programming a cell to target tumor cells. First, the delivery of VSV-G (vesicular stomatitis virus glycoprotein) allowed the cell to undergo membrane fusion with adjacent cells to form syncytia (i.e., a multinucleated cell) in conditions of low pH typically occurring at a tumor site. The formation of syncytia caused the clustering of nuclei along with an integration of the microtubule network and ER. Interestingly, the formation of syncytia between cells that are dynamically blebbing, a mode of migration preferred during tumor metastasis, resulted in the loss of these morphology changes. Lastly, the codelivery of VSV-G with L57R (an engineered photoactivated caspase-7) allowed cells to undergo low pH-dependent membrane fusion followed by blue light-dependent apoptosis. In cell-based therapies, the clearance of syncytia between tumor cells might further trigger an immune response against the tumor.
authors: Seema
authors: S
authors: Nagaraj
authors: Evan
authors: E
authors: Mills
authors: Stanley S C
authors: SS
authors: Wong
authors: Kevin
authors: K
authors: Truong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D019556:COS Cells; D053179:Caspase 7 / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000502:physiology; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000235:genetics; D015726:Giant Cells / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics; D057688:Transcellular Cell Migration / Q000235:genetics / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D053179:Caspase 7